After the Chief announces his retirement, rumors begin to circulate on his departure and successor. Mark is determined to leave Seattle for good but Meredith accidentally has him stay after letting him know of the open Chief position. 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. The attending physicians at Seattle Grace Hospital fight to get Richard's attention, but he expresses his disappointment. 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. George, devastated after his father's death, uses sex to overcome his grief, and eventually proposes to Callie. Cristina and Burke still don't speak to each other, but he breaks the agreement when he proposes to her. Richard endeavors to reunite with his wife, Adele, and decides to retire, only to come home and find his wife with another man.

Meredith works on her relationship with Susan and Thatcher. Cristina has to deal with her mother and Burke's. Alex continues to tend to Jane Doe/Ava. Meredith and Derek's relationship has a problem that needs resolution quick. Addison sees her god-daughter which leads to a job offer outside of Seattle. Derek has to perform surgery. Burke has a reservation about marrying Cristina. Many new people guest star in the course of Addison's road trip to California. Addison considers moving to be closer to her old med school friends until she discovers that drama she wishes to leave behind isn't exclusive to Seattle. Her friends who she thought had it all, are divorced. A pregnant woman must discover who the father of her child is.

Meredith works on her relationship with Susan and Thatcher. Cristina has to deal with her mother and Burke's. Alex continues to tend to Jane Doe/Ava. Meredith and Derek's relationship has a problem that needs resolution quick. Addison sees her god-daughter which leads to a job offer outside of Seattle. Derek has to perform surgery. Burke has a reservation about marrying Cristina. Many new people guest star in the course of Addison's road trip to California. Addison considers moving to be closer to her old med school friends until she discovers that drama she wishes to leave behind isn't exclusive to Seattle. Her friends who she thought had it all, are divorced. A pregnant woman must discover who the father of her child is.

Entering their first year as residents, Meredith Grey, Cristina Yang, Izzie Stevens and Alex Karev now have interns of their own to mentor. Among the new interns are George, forced to repeat his internship after failing his exams, and Lexie Grey, Meredith's half-sister. Another two new interns will be introduced in this season premiere. And they'll have their hands full when a three-car accident sends multiple casualties pouring into Seattle Grace. Some of the doctors need to deal with new stressed out interns. A young boy brings his bleeding deer to the hospital in the hope a doctor will save her.

An ambulance crash endangers the lives of the paramedics involved, as Meredith and the Chief work on-site to save them, Bailey treats a patient who refuses her help, and Ava returns for Alex and meets his other girlfriend in the process.