

In the aftermath of Izzie's affair with George, he doesn't seem to remember anything. Izzie wakes up, realizing that she has slept with George while they were both drunk. She seems to connect with Susan, but her relationship with Thatcher seems to be irreparable. He moves in with Meredith and they have a dinner with her father and stepmother. Alex continues to work with Jane Doe, whose memory doesn't seem to come back.

Derek treats his former colleague from New York, and forces her to have surgery for brain cancer in order to save her future, no matter what the post-surgery risks are. George finds out that Callie's family is rich, but she had previously hidden the fact in order to find out whether George loves her for who she really is. He begins to lie to Burke in order to protect her secret, but is soon faced with the realization that their relationship is on the rocks. They soon realize that the new surgeon, Colin Marlow, was Cristina's professor in medical school and they used to have a long-term relationship. The race between the attending physicians for the Chief of Surgery position heats up after a new competitor enters the fray. Richard talks to Ellis and realizes that she is still in love with him, but loses her memory after their talk ends, before Meredith has the chance to tell her how she really feels. Ellis has to have heart surgery and, despite her wishes, Meredith schedules her upcoming surgery. She is disappointed in the mediocrity her daughter has fallen into and begins to despise Derek, blaming him for what happened to the Meredith that used to be "a force of nature". Meanwhile, Meredith's Alzheimer's-stricken mother, Ellis Grey, experiences a change in her medical condition by becoming lucid for the day. Izzie is not supportive of their marriage and tries to get George to realize the mistake he has made. Callie and George get back from Las Vegas, announcing their marriage, much to everyone's disbelief. Izzie is disappointed in what she invested Denny's legacy in, and tries to steal patients from the emergency room. The Denny Duquette Memorial Clinic is open for business, but only one single patient shows up. The race for the Chief's position is on, and the attending physicians, Derek, Burke, Addison and Mark, compete for Richard's affections by trying to help out everywhere possible. Richard endeavors to reunite with his wife, Adele, and decides to retire, only to come home and find his wife with another man. Cristina and Burke still don't speak to each other, but he breaks the agreement when he proposes to her. George, devastated after his father's death, uses sex to overcome his grief, and eventually proposes to Callie.
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He also displays his lack of support in Bailey's plan to create a free medical clinic, but she ultimately goes through with her plan when Izzie offers to spend her entire 8.7 million dollar inheritance on the project. The attending physicians at Seattle Grace Hospital fight to get Richard's attention, but he expresses his disappointment. Derek is angry at Meredith for causing Mark to stay in Seattle, but soon realizes that she is not the reason he is really angry. Mark is determined to leave Seattle for good but Meredith accidentally has him stay after letting him know of the open Chief position. After the Chief announces his retirement, rumors begin to circulate on his departure and successor.
