Meredith and Derek find that "happily ever after" isn't as easy as they hoped, Cristina finds interest in a military doctor, and the Chief is surprised to hear that Seattle Grace is no longer ranked as a top-tier teaching hospital.
As a group of best friends deal with the aftermath of their car crash, Dr. Torres takes the lead on a groundbreaking course of treatment for one of the patients. Meanwhile, Major Hunt starts to irritate other attendings with his presence in the hospital.
Determined to reverse Seattle Grace's slide into mediocrity, the chief lays down some new rules for interns and residents with which no one's happy. Derek asks Meredith for further changes in her living arrangements. Lexie challenges Cristina's diagnosis for a patient with a persistent headache, and the chief's preoccupation with reputation blinds him to problems with the physical plant.
Bailey's dream of a domino surgery is scuppered when one of the donors learns of her husband's affair, and Meredith is insulted when she gets no credit for the procedure she and Derek worked on together.
Derek has trouble with objectivity concerning his death row patient, Cristina and Meredith continue their feud, Izzie confides her problem to Alex, and the Chief faces what's become of his life's work.
Cristina carries on an intense flirtation with Owen, Derek gets advice from everyone on how to propose, Izzie gets some tests done, and Bailey's promotion may stand in the way of a new career possibility.
Owen runs into someone very special from his past. Izzie employs her fellow doctors in a medical game made to help teach the interns. Naomi, Sam and Addison rush Archer to Seattle Grace and meet with Derek and Mark to save his life.
Derek's malpractice deposition reveals an unhappy statistic, the interns finally diagnose 'Patient X', Karev stands up to two attendings to save a band geek, and when Webber shuts Miranda out completely she makes a call.
Sloane's facial transplant fades to the background as the interns begin squabbling, Bailey's attempts to reach Derek unexpectedly clear surgeons from the hospital, and Cristina juggles her first solo surgery with treating a resistant Izzie.
Izzie bites off more than she can chew on her first day of chemotherapy, Mark and Derek are forced to work on the same patient, Meredith's plans for a simple wedding take a turn, and Karev finds himself split between worry over Izzie and excelling as a resident.
A car crash involving students going to their college graduation takes its toll on the residents in the ER, Derek's wedding gift is uniquely suited for Meredith - even if the oversight is not. Meanwhile, Denny's return has Derek and Bailey searching for the cause, and the results will change the outcome of the day.
Izzie is torn over whether to have Derek's proposed brain surgery. A soldier on medical leave asks for a radical operation so he can return to active duty. The Chief tries to lure Bailey back to general surgery with a new toy, and Mark shifts into high gear with major life changes.