Event Year: 2005

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.

Derek and Meredith try (unsuccessfully) to be discreet as they spend the night together at Meredith's house, but their haggard appearance speaks volumes to everyone – including Bailey, who warns Meredith to end the relationship. Meanwhile George suspects an anesthesiologist of drinking on the job but is reluctant to speak up about it, Alex treats a former competitor who now finds honor in self-mutilation, Izzie has to deal with a patient who won't let go of his girlfriend – literally, and Cristina seems to be battling a case of the flu.

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 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.