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.
Covering days one through 13, everyone at Seattle Grace fights to save Izzie and George's lives and then deals with the aftermath. Elsewhere, Hunt treats a double amputation, and Arizona has a teen with painful growth spurts.
Thatcher is hospitalized with liver failure, and Meredith fights anger and guilt while deciding her responsibility. Sloan treats an octogenarian who wants an implant. Izzie's interference in Hunt's cancer case may have deadly consequences.
After a burn victim unexpectedly dies in the midst of a chaotic ER, the Chief and board member Jennings interrogate the residents to find the culprit, as all the Mercy West and Seattle Grace residents defend their actions in an effort to save their jobs.
When Isaac, the hospital lab tech, has an inoperable tumor wrapped around his spine, he turns to Dr. Derek Shepherd to do the impossible, and Derek tests the Chief's authority when Richard objects to moving forward with the risky surgery.
A generous donation is offered to Seattle Grace by the parents of Arizona's 10-year-old patient. When his condition worsens, however, she finds herself with a conflict of interest. Meanwhile, Cristina tests her boundaries with Owen at the hospital and, adding insult to injury, Alex is left with all of Izzie's hospital bills to contend with.
When Owen recruits his fellow Iraqi War vet, Dr. Teddy Altman, as the new cardiothoracic surgeon, Cristina questions Teddy's abilities in the OR and the nature of their past relationship. Meanwhile Izzie returns to Seattle Grace with her high school mentor seeking treatment for his dementia, and the stress of Richard's responsibilities, post-merger, are taking their toll.
As Thanksgiving, Christmas and New Year's pass, Miranda is visited by her father, William, who disapproves of her choices in life; meanwhile, Mark and Lexie must cope with the shocking arrival of a woman from his past, and Thatcher Grey questions the Chief's recent behavior as Meredith comes to his defense.