A nurse tends to Eddie Novack as he lies dying in his bedroom. Through strained breath, Eddie apologizes to his wife Charlotte for not taking her to Rio before he passes. Suddenly, Charlotte can't breathe and starts choking from acute respiratory failure. Eddie calls for the nurse to help.
Taub and Foreman present Charlotte's case to House, but he's already dismissed that the patient's obesity is the cause. He asks about the whereabouts of the missing teammates. Taub says Thirteen is with Charlotte and Kutner is late because of his sick dog. Foreman turns the conversation back to the patient, who has been tending to her husband's heart failure for the last six months. Thirteen enters with the news that Charlotte wants to be released so that she can be with her husband who has gotten stronger since she stopped breathing.
Taub wheels Eddie into Charlotte's room, hoping that his presence will help heal her. Meanwhile, in the clinic, House stares at Rosabel, a six-year old beauty queen who is woozy. Her mother Katherine is urging House to make a diagnosis because they have a pageant to get to. House quickly sees that Rosabel is drunk, and can smell mouthwash on her breath. The girl says that her mother drinks mouthwash too.
Charlotte's breathing returns to normal. She can be discharged. Yet House is more concerned with why Kutner still hasn't shown up to work, and accuses Taub of covering up for his friend.
Charlotte starts to suffer extreme chest pain. Taub rushes in to find Eddie stable, so he listens to Charlotte's chest. There is no fluid in her lungs and Taub has no idea why she is reacting.
Foreman and Thirteen go to Kutner's apartment to look for him. They find Kutner lying in a pool of blood. A gun is by his side. They try to revive him and call for an ambulance. With Kutner's body cold, they give up.
The team assembles silently in House's office. He asks if Kutner said anything about family problems, bad relationships or financial pressures. Foreman notes that Kutner's parents had been shot right in front of him as a boy. Yet this was long ago, and House says that shooting yourself is an act of panic. He suggests that Kutner's co-workers should have seen something coming. Thirteen is angry at being held accountable, and reminds them that suicidal people show no outward signs of depression. Taub calls Kutner an idiot and claims to feel no guilt. He'd rather they deal with their patients, but Foreman wonders whether they should pass the case on for the time being. House re-focuses them on the case. As they start to list possible causes for Charlotte's illness, Cuddy enters the office to announce that she has hired a grief counselor and that they can all take time off. She knows none of them will take up either offer. House says that polyserositis fits Charlotte's case and orders the team to start her on indomethacin.
Cuddy is surprised that Wilson hasn't come to talk to House yet. House says he had no inkling of what was happening to Kutner. She apologizes for his loss, but House says it's not his loss. "Then I'm sorry you don't think it is," she says.
As Taub gives Charlotte the non-inflammatory, Eddie awkwardly tries to make his wife imagine being in Rio. She says she refuses to go without him.
House, Thirteen and Foreman visit Kutner's adoptive parents, Julia and Richard. They show photos of Kutner as a child and recall when he came to live with them after going through a tragedy at such a young age. House tells them that Kutner had no idea what his identity was supposed to be. He was immersed in an Anglo world when he was born Lawrence Choudhary. Julia explains that they tried to encourage him to retain his heritage and that it was Kutner's idea to take their last name. Yet House presses on, accusing the parents of shutting out their son's pain and not understanding him. Julia begins to tear up and Richard's anger rises. Foreman yells at House to leave, which jars House from his rant.
House returns to the hospital, and Taub meets him at the elevator to brief him on Charlotte's progress. He also ran a hormone test on Eddie, who is improving. Taub theorizes if perhaps the couple's love changed their body chemistry. House isn't interested, and questions why Taub hasn't asked if he learned something from the Kutners that might have saved him. "Sometimes you just don't want help," Taub says. House busts Taub that he got help or else would have tried again and gotten it right. Taub continues the conversation back onto the patient, stumped that nothing fits any diagnosis.
House goes to the patient room to suggest they induce a heart attack in Charlotte because her heart is too strong while Eddie's is too weak. This scares the pair, so House then accuses Charlotte of faking in order to cause Eddie to hang on for her. She admits to doing this because she loved being so close to him recently. Suddenly, Charlotte cries out in leg pain. House is annoyed, but then sees her one leg is extremely thinner than the other. Pressing it causes a deep indentation.
The team discusses this new symptom that would make muscle disappear. Foreman is still furious with how House treated the Kutners, but House can't figure out what caused him to commit suicide. He has called all of Kutner's friends, who had nothing to offer. Taub again tries to force them back onto the patient, but House goes to leave, telling them to test Charlotte for Multiple Sclerosis and run an echo on Eddie's heart.
House goes to Cuddy with Kutner's personnel file that he stole from her office. He wants to know why she hired Kutner when he was charged with indecent exposure. Cuddy answers that Kutner only streaked at the Penn-Dartmouth game, which is what House would have expected of him. When House is frustrated that it wasn't a lead on an answer, Cuddy tries to comfort him and says he should be upset because Kutner was similar to him.
Thirteen performs an MRI on Charlotte, who admits that Eddie never really showed affection or spent time with her. Suddenly Charlotte crashes. Meanwhile, Taub runs an echo on Eddie, who confesses that he wished he had more time to spend with his wife and make up for the past. Taub sees that Eddie's heart chamber walls are barely moving. This is not a good sign.
Cuddy comes to Wilson and asks him to be House's friend. He lambastes Cuddy for wanting him to be the one to take care of House. Then she says that House told Kutner's parents that it was their fault. This leaves Wilson speechless.
Chase operates on Charlotte's ruptured spleen, which means it wasn't MS. Taub waits impatiently for the organ so that he can biopsy it for rheumatoid arthritis. Chase says he can do it and that Taub should go home and mourn for his friend. "Kutner wanted to die," Taub says, refusing to leave. Chase notices that the liver is scarred, so it's not rheumatoid arthritis, but the surface is rough and bumpy. Whatever Charlotte has is spreading.
Wilson goes to Kutner's apartment, where House is alone. "Good to see you," House says before explaining that he's looking for whatever Kutner was hiding. They look at Kutner's collectables and House comments that Kutner had passions. House knows that Kutner was open about his pain and wouldn't have hid it. With House still searching for what he might have missed, Wilson realizes that House doesn't care about Kutner -- he cares about solving the mystery. House surmises that he didn't miss anything because Kutner was murdered. Wilson becomes disgusted with House and with himself for giving in and coming there. He leaves House alone among the death scene.
The next morning, the team goes over Charlotte's case. Foreman is missing, taking Cuddy's offer of time off. They eliminate hepatitis because Charlotte's thyroid is normal. Taub reluctantly admits that Eddie's heart is still failing and he was wrong about their health being connected. House turns the white board around so the others can see. Instead of listing possible diagnostics for Charlotte, he's written potential motives for Kutner's murder. Thirteen is appalled and refuses to indulge him. House thinks she's mad because Foreman called him about taking time off before calling his own girlfriend. Even Taub charges House for embracing the irrational. Frustrated with having no allies, House orders them to run the patient's AAT proteins to look for an alpha-1 anti-trypsin deficiency.
As Taub draws her blood, Charlotte asks to donate her heart to Eddie even though donor banks have turned him down. Meanwhile, Thirteen goes to see Foreman at his apartment, and he says he needs time alone. He's always worked through issues by himself. She's upset, but leaves.
Cuddy comes to House's office because he is logged onto Kutner's email account. House theorizes that the man who killed Kutner's birth parents is coming up for parole and may have enlisted someone to get rid of Kutner. Exasperated, Cuddy reminds him that Kutner's fingerprints were on his own gun. House still believes the murderer would make it look like suicide. He also lets her know that he is aware she is checking up on the patient's case because she thinks it's the only thing holding him together.
Taub and Thirteen rush to treat Charlotte, who broke into a cart to inject herself with whatever she could grab. Taub tells a stunned Thirteen that Charlotte was trying to kill herself. Later, as a restrained Charlotte is kept stable, Taub reports to House that the patient's liver is now more damaged and she tested negative for AAT deficiency. She needs a new liver within twenty-four hours but the test for myelofibrosis to prove she requires a transplant takes forty-eight hours. House fills out the form with the diagnosis in a lie to the transplant committee. His cell phone rings, but Thirteen takes the phone from him, refusing to let his fixation on Kutner interfere with treating their critical patient. House has a realization, and leaves the office.
House goes to Cameron in the ER. "I need an incurable romantic to talk to an incurable romantic," he says before Cameron interrupts him by insisting that Kutner wasn't murdered. She knows he wants this answer to let himself off the hook. House needs her to convince Eddie to donate his liver to his wife, which means that he will die on the operating table.
Cameron speaks with Eddie and explains that they can't tell Charlotte what they are planning. He only has a couple of days to live with a weak heart, but at least it will help his wife survive. Eddie accepts his fate and signs the consent form. She watches his fingers closely.
Cameron tells House that he cannot perform the transplant because she noticed that Eddie's fingers have nodules. She thinks his doctors misdiagnosed him and what he has is curable. House refuses to listen to her even though this result would allow him to prove other doctors are idiotic. He begrudgingly admits that the guy who killed Kutner's birth parents died two months ago. Cameron knows this mattered to House, and says that no one got a chance to save Kutner. He should try to save Eddie instead.
Later that night, House lets Eddie know that he figured out that his heart failure was caused by a fungal infection called cardiac blastomycosis, which is treatable. He got better earlier because his emotional state helped temporarily raise his prolactin. Yet Eddie doesn't want the treatment. He'd rather give up his liver to allow his wife to live even though it's not certain she will survive the transplant. Eddie is adamant and threatens to get "hit by a car" so that his body will show up in the morgue to allow her to have the organ.
House sits, resigned, in his office as Thirteen questions why they should commit murder. She won't do it, but Taub says he will. "We've already had one pointless death," he sighs.
Taub wheels Eddie's bed into Charlotte's ICU room. He tells her that Eddie has a curable disease but wants to die in order to give her his liver. Eddie is furious, and Charlotte is overcome with emotion. Eddie pleads with her to let him do this to make up for things. Yet Charlotte shakes and becomes unresponsive.
Taub briefs House that Charlotte's body has become infected all over. Her white blood cells are elevated and she has a fever. Thirteen interjects that infection is a new clue. They run through possibilities, but House remembers Charlotte was a neglected housewife who always wanted to go to Rio. He rushes to the ICU room, followed by Taub, and asks Charlotte about her trip to Rio. They have disease-bearing sand flies there, which means she has visceral leishmaniasis. Charlotte admits to Eddie that she got tired of waiting for him and went to Rio with another man.
House tells Taub to have Cuddy find Charlotte a liver donor. He adds that the couple was ready to die for guilt, not love. Taub says that you cannot feel that much guilt without love.
The next day, Taub lets Cuddy know that Charlotte's treatment isn't taking and that they diagnosed it too late to transplant a new liver. She offers him a ride to Kutner's funeral, but Taub would rather stay with his patient. Cuddy tries to be sympathetic that Charlotte bought them some time to save Eddie, which will give her death meaning, but Taub bluntly says it won't.
As House stares at the white board of murder reasons, Wilson comes to see him. He knows House is in pain because he is terrified of losing his gift. House never saw Kutner's suicide coming even though he sees EVERYTHING coming.
A pundit presides over the Hindu funeral for Kutner. Thirteen, Cuddy, Wilson, Chase and Cameron stand together. Thirteen sees Foreman standing alone in another aisle, lost in his private thoughts. They are among the pallbearers who carry the casket to the crematorium. Foreman comes up to Thirteen and takes her hand. She looks to him, but his face watches the smoke rising into the sky.
In the hospital, Eddie kisses the jaundiced hand of Charlotte. She reacts to this kindness before flat lining. Taub retreats to a hallway bench alone. He sits and cries.
House returns to Kutner's apartment, still searching for answers among the personal items strewn about. House goes through photographs. They all show a smiling, happy Kutner through the years. One photo catches his eye. It's a candid shot of Kutner looking away from the camera. While neither happy nor sad, it's different from the others. House sits on the bed, staring at the photograph. He's still uncertain and without answers.