Everyone reminisces about the past. Meanwhile, Izzie is emotionally devastated, with the others trying to help her, Adele gives Richard an ultimatum, and George and Derek are put in quarantine when an outbreak of the plague is suspected.
Izzie copes with her grief by baking furiously, and George has to deal with an obstinate patient. Meanwhile, Meredith must choose between Derek and Finn, Addison drowns her sorrows in alcohol, and Cristina meets Burke's difficult mother.
Izzie returns to the hospital, but finds it difficult to go inside, and George is tired of Callie's presence at home. Meanwhile, Addison cannot seem to get rid of Mark, and Cristina tries to cope with caring for Burke.
Meredith becomes a patient, and Derek and Addison are equally angry at Richard for allowing Mark to join the staff. Meanwhile, Izzie receives a visit from Denny's father, and Burke is plagued by doubt over his ability to return to surgery.
Izzie returns to the hospital under probation, and George tries to make amends with Callie. Meanwhile, Cristina's deletion of Bailey's name on Burke's OR board makes her assume he is against her, and Derek's irritating sister Nancy visits.
Derek, George, Alex, Burke, Richard, Joe and Walter go on a camping trip. Meanwhile, Meredith assists Mark with gender reassignment surgery, Izzie avoids discussing her grief, Addison works with Callie, and Cristina feels Bailey's wrath.
George must deal with his family's presence when his father is admitted. Meanwhile, Burke's secret is almost out, Alex tries to get close to Izzie again, and Richard comes to a decision about his marriage.
A traumatic car accident fills the ER. Cristina has a crisis of conscience about her deceptive teamwork with Burke, Izzie pushes the boundaries of her probation, and Callie tries to explain herself to George.
Bailey is adamant that Burke and Cristina should be punished, Derek doubts his abilities, Izzie tries to takes a stand against Mark's patronizing behavior, and Meredith deals with family in two very different ways.
As George's father's surgery approaches, he begins to realize how serious his condition is. Meanwhile, Izzie has to prove to Bailey that she is ready to scrub in on a surgery, and Meredith keeps running in to her father.
George deals with his grief, Cristina and Burke continue to ignore each other, Addison avoids Alex, and Izzie decides to help Bailey with a project. Meanwhile, Richard makes a decision which sends all the attendings scrambling.
A toxic patient wreaks havoc. Meanwhile, Bailey opens the free clinic, but the lack of patients makes Izzie question her investment. Meredith's mother is admitted again, and Cristina makes Burke wait for an answer.
The interns each react differently to a mass-casualty incident. Meanwhile, George crosses the professional line with Callie, Cristina asks Burke to keep quiet about their engagement, and Richard dons a new hairstyle.
Izzie fights to save her patient's life, George searches for the son of his patient, and Alex has to contend with the relatives of victims. Meanwhile, Meredith is unconscious underwater, with Derek her only hope.
An unconscious Meredith interacts with some ghosts from her past while Richard, Burke and Bailey devise an unusual method of reviving her. A despondent Cristina leaves during her shift, and Derek speaks his mind to Meredith's mother.
A Korean war veteran with a bullet lodged in his shoulder is admitted. Meanwhile, tensions escalate between Izzie and George, Callie reveals a big secret, Cristina contends with an old flame, and Alex continues to work with the Jane Doe.
The attendings face their board interviews. Meanwhile, Izzie seems to be the only one who remembers the night before, Derek is overly protective of Meredith when Mark offers her a surgery, and Callie's father pays a visit.
Meredith deals with her over protective stepmother, Cristina is caught between Burke and Marlow, and Derek fights to become Chief. Meanwhile, Alex continues the search for Jane Doe's identity, and Izzie's past comes back to haunt her.
The Chairman of Seattle Grace's board of directors is admitted, and the attendings vie for his favor, while the interns study for exams. Izzy and George are reminded of their infidelity, and Burke presses Cristina about wedding plans.
Addison heads for warmer climes to figure things out, Meredith's stepmother visits the clinic, Cristina's perfect wedding is challenged when she and Burke's mothers visit, and Izzie tries to talk to George.
Addison is pulled into the case of a high-risk surrogate mother, Meredith's stepmother develops a complication, Izzie struggles with George's decision, and Ava has surgery which may restore her memory.
The interns face their first year medical exams. With the interns busy, the attendings must do their own legwork, Burke appoints a new best man, Cristina writes her vows, and Callie grows suspicious of George and Izzie.
The wedding day arrives. Richard chooses the new Chief and Chief Resident, the interns receive their exam results, Callie drops a bombshell on George while Izzie pours her heart out to him, and Burke makes an important decision.