A bike race injures several pedestrians as well as well as participants. One pedestrian is left brain dead. Christina and Issie wish to use his organs for organ donation but with Christina's detachment and Issie's ever hopeful attitude that the man will recover, they will find the organ harvesting process an emotional one. Preston faces feelings of his dislike of organ harvesting - as a surgeon, he likes saving lives; harvesting organs doesn't save the person's life. George deals with Mac, a friend of the chief, who won't stop flirting with him. He is in need of a new liver. Meredith is fed up with Alex showing off as she continues trying to push Derek away. She also is reaching the limits of Issie's sunshine and George's politeness as she goes on living with them. Then there is their desire to see Meredith's mother's medical tapes. Getting through the day, Meredith realizes the keys to winning the race.

Meredith realizes that she must take on a lot more responsibility when she is told that her mother needs to sign over all of her assets to her. As Izzie prepares to have a party for her boyfriend Hank (the scale of which is unknown to Meredith), Meredith has her first heart surgery. During the surgery she fears that she has fallen asleep and damaged the patient's heart. Meanwhile, Cristina and Burke hit it off. At the party, Meredith and Derek get caught together by Dr. Bailey.

Izzie tries to get George to find the courage to ask Meredith out. All of the interns are in awe when a woman comes in with a record breaking tumor, but it is so far advanced that the woman's prognosis is not good. Now that Bailey knows about Meredith and Derek's affair, their jobs are in jeopardy, and she advises Meredith to end it. Meanwhile, Cristina and Burke's secret relationship is also getting more complicated...

Meredith grows increasingly dissatisfied with the unknown details of Derek's life. Meanwhile, Alex treats Devo, a patient whose religious beliefs jeopardize her chances for recovery; Izzie contemplates reconnecting with her estranged mother; Zoey, a pregnant woman in her 40s who's been diagnosed with cancer, disagrees with Cristina's medical advice; and the interns are mystified by Cable, a patient who's being treated for seizures and who thinks he's psychic.