The big day has arrived and Izzie is ecstatic about attending the "perfect" wedding she's planned for Derek and Meredith.
Meredith is excited to get married, but not about the wedding itself. "It's the biggest day of Izzie's life, not the biggest day of my life," she tells Cristina. As Derek says of the elaborate church ceremony neither he nor Meredith wanted: "We're just the bride and groom. It has nothing to do with us."
There's a setback for Izzie, however: She's started seeing Denny again. Miranda does an MRI and finds nothing, but Izzie insists they look closer. Derek finds a way to map her brain while she's having a hallucination. When Denny appears to her, Derek is able to pinpoint a tumor too tiny to show up on an MRI -- and too tiny to operate on.
Callie, who's now penniless without her trust fund, is taking extra shifts in the ER to make ends meet. She tells George and Alex it's "slow," but then the phone rings with word of an enormous accident: A semi has rammed into a bunch of college students bound for their graduation. While dealing with the incoming injured, she has to dodge Arizona, who wants to know why she was so distant the night before at dinner at Seattle's most expensive restaurant. Callie would rather break up with Arizona than admit the truth. But when Arizona confronts her, she is finally forced to confess, "My father cleared out my bank account and I am broke." Arizona vows to stay in and eat sandwiches with Callie instead of dining in pricey restaurants.
George and Lexie have their hands full trying to deal with the victims of the accident, and George is crushed when he doesn't manage to save even one patient. The only one who lives is one that Owen worked on. Owen tells George that his teamwork enabled him to save that patient, "Trauma's a team sport. You don't have to be a hero, you just have to go where you're needed."
Just before she goes into surgery, the class valedictorian begs Alex to tell her whether her friends are dead, saying she can handle it. He doesn't want to tell her that they're all gone. Instead, he asks her to give the graduation speech she had planned.
Owen tells Cristina that his therapy is going well but slowly. He now knows that it was her ceiling fan that was the trigger when he attacked her: It reminded him of the blades of a helicopter. He goes to take her hand but she moves away. Later that night, however, she takes down the ceiling fan.
Derek gives Meredith a wedding present: Her first solo surgery, which Richard oversees, hovering closely. Richard tells Meredith her mother would have been proud. "She wouldn't have been able to tell you, but she would have been thrilled," Richard says.
Derek is deeply saddened that Izzie's tumor is inoperable. "I wish there was something I could do for her," he tells Miranda, who says, "I know something you can do." Meredith thanks Derek for her wedding present and he asks her, "What do you say we make this day even better?" She goes to find Alex who is sobbing: "I think she's going to die on me." When Alex wonders why she's not getting ready for her wedding, Meredith replies, "That's what I came to talk to you about."
The would-be bride shows up at Izzie's hospital room with the wedding dress, saying, "This dress is not for me." Izzie is upset, thinking that Meredith has gotten cold feet, but Miranda explains that the dress is really for Izzie. Puzzled, Izzie looks up to the door to see Alex dressed in the wedding suit she picked out for Derek.
The two of them take Derek and Meredith's place as bride and groom in the beautiful ceremony that Izzie had planned, with George giving Izzie away. Izzie hasn't written any vows, but Alex has: He's inspired by the speech the college valedictorian was going to give that starts off, "Today's the day my life begins..."
Izzie is a beautiful, glowing bride, but back at the hospital, she's alarmed when her hair starts falling out. Alex tells her it's no big deal and that she'll still be beautiful even when bald. Alex goes to get some champagne and Izzie tells Denny how today was the biggest day of her life. When Alex returns, she tells Denny, "Go away. I want to be alone with my husband."
She takes off her scarf to reveal her newly shaved head. "My wife is hot," Alex says proudly.