A young boy needs a heart transplant but doesn't seem to want it, and an argument over his treatment exposes major philosophical differences between Burke and Cristina—he's spiritual, she's not. Burke won't operate on the boy until his mind accepts the heart, because he believes the body will reject it if he doesn't. Cristina, though not a believer, makes a connection with the kid over their shared skepticism, and gets the boy to want the heart.

Meanwhile, when the interns rally to help Alex prepare to re take his exam, Izzie feels betrayed (after all, Alex just cheated on her). Meredith has to remind Izzie of the true spirit of the Christmas holiday.

Derek and Izzie treat a father who has a major attitude change after brain surgery the family thinks that Derek may have broken their dad, and Izzie doesn't necessarily disagree.

George and Bailey deal with a woman needing minor surgery that keeps getting her surgery delayed. The woman's family is loud, obnoxious, and crazy, and George has to really stand up to them at the end.

As for Derek, despite a reconciliation with Addison, Derek isn't in a festive mood. Christmas is about being with the one you love, and he doesn't think he's with that person.