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.
Mark flies Addison to Seattle to help with a difficult procedure on his pregnant daughter, Sloan. Owen questions Teddy's motives when she assigns Cristina the lead on a complicated surgery, and Derek's suspicions are raised when the Chief recruits Meredith to assist with a high profile operation.
After learning of Richard's drinking problem, Derek confronts him for the sake of his friend and the hospital, Izzie returns, hoping to reconcile with Alex, and tensions run high between Teddy, Cristina and Owen in the aftermath of Cristina's startling confession.
An intra-operative crisis casts a shadow over Derek's first day as interim chief, Owen's influence worries Cristina, Karev's first pediatric surgery case turns out to be more than babysitting and Webber resents the decision he must make.
It's Valentine's Day and the doctors must treat dozens of injured people after the roof collapses at a popular romantic restaurant; Derek tries to manage his busy schedule as Chief of Surgery; Meredith wrestles with her new duties as the Chief's wife; and Mark and Callie team up to convince Sloane to do the right thing for her baby.
In his new role as Chief, Derek restores the hospital lecture series, and several attendings present to the group pivotal surgical cases from their pasts: Bailey reflects on how shy she was as an intern until getting advice from Webber, Callie looks back on a polio case, and Richard recalls a case in which he and Ellis worked on a patient diagnosed with AIDS, known in 1982 as GRID.
When Avery's grandfather comes to the ER, Webber's wish for a stress-free first day back is lost after the surgeon requests an awake surgery. Elsewhere, Cristina and Teddy attempt a hand-me-down lung transplant for a cancer survivor.
A patient who needs an extremely difficult surgery comes to Seattle Grace, and it's Richard and Owen who vie for the opportunity to tackle it. But the decision lies in the hands of Derek, who deems that Owen should take on the surgery, leaving Richard bitter. Meanwhile, Bailey deals with her own personal struggles when she nervously prepares for another date with Ben.
When Teddy's patient seeks to end treatment and her life, she turns to Hunt for help. The situation triggers Hunt's memories of his life at war and his past relationship with Teddy. Meanwhile, Callie and Arizona have a difference in opinion on what their future holds, and Richard tries to adjust to his role as a surgeon.
Sloan returns to Mark's apartment, just as she's going into labor, and Teddy, Mark and the still-fighting Callie and Arizona are there to help with the birth and to get Mark through his grandson's pending adoption. Meanwhile Teddy sees Derek's invitation to illustrious cardiothoracic surgeon Tom Evans' as a threat to her future employment at the hospital, and the team work on a crab boat captain who has been stabbed with a giant shark hook.
Bailey preps the team with mandatory sensitivity training prior to admitting a 700-pound patient with compounded medical issues, and the case proves to be challenging. Meanwhile Derek has to come face to face with a former patient's husband in a wrongful death deposition, and spending time with a heart patient's daughter opens up some old wounds for Cristina.
An elderly patient admitted into the E.R. for a heart condition sees a familiar face, a long lost love who happens to be in the E.R. as well for a fractured arm, and the staff find themselves caught up in their love story. Meanwhile, Karev treats a troubled teenage patient whose parents brought her in for schizophrenia, and Meredith can't help but tell Cristina about her suspicions of Owen -- which inevitably messes with Cristina's head.