Josh wandering through the woods, apparently out for an evening stroll. Disrobing, he stands alone, naked, waiting for something, or someone, but what?
Back in town, the dark and handsome Aidan is at the end of a lovely date with Rebecca, his beautiful redheaded co-worker, who invites him in for a nightcap and possibly more. The night takes a sinister turn when Josh transforms into a werewolf and Aidan gives in to his vampire urges and bites Rebecca during sex. The morning finds a blood-smeared Josh lying next a slaughtered deer that he must have killed as a werewolf. Aidan's kill is much more significant: Rebecca never wakes up. He calls Bishop, the local vampire leader, to help him cover up the murder.
Later, at the Boston hospital where Aidan and Josh work, Aidan broaches the subject of the two of them living together for moral support and camaraderie. Josh is doubtful that it will help but he eventually agrees. When they finally find a place they discover that Sally, the gorgeous former fiancée of the landlord, is haunting their new home as a ghost. She's elated that they can see and hear her- she's been incredibly lonely since her death. After some initial tension, the three form an uneasy alliance to help each other assimilate into the world of human beings.
Living together doesn't make their lives any easier, though. Soon, Aidan sees Marcus, Bishop's number two, lurking in the halls of the hospital, searching for prominent humans to turn into vampires. Aiden fights with him, telling him that the hospital is off limits for recruiting, but Marcus knows that's Bishop's decision to make, not Aidan's.
It isn't long before Bishop comes to visit Aidan and seduce him back in the life he once loved as a predatory creature of the night. Aidan wants to stay clean and live peacefully amongst humans but it's hard to undo the habits he's formed over hundreds of years of being a vampire. It certainly doesn't help matters that Cara, Rebecca's replacement, is interested in him.
Meanwhile, when Josh's sister Emily shows up at the hospital with her girlfriend, Josh is forced to face the life he left behind two years ago when he was first turned into a werewolf. Emily tells him that his family and friends think he's dead and she's desperate to know what made him leave them all behind.
Emily's curiosity leads her to follow Josh as he sneaks into a remote room of the hospital's basement where he hopes to transform into a werewolf without hurting anyone. But when Emily gets locked inside the room with Josh just as he begins to transform, only his supernatural roommates can keep him from inadvertently killing her.