Event Year: 2005

A face familiar to one of the year-twos shows up and dredges up issues that were never really dealt with. A teen soccer player needs counseling because of his father and surgery for an injury he sustained while playing the game. Another patient's, named Courtney, finds out that her cancer is back.

A patient is in the hospital because they fell asleep in a hazardous situation. A patient's home laboratory blew up in an apartment building and the victims flood the hospital. Alex investigates the cause of the incident by talking to a really old guy who lived in the building. Jane Burke shows up to deal with what her son left behind. Lexie tries to talk to Meredith. Callie is overwhelmed by her new position while Bailey is searching for things to do.

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.

The mountain climbers lie about the axe in their friend's head, telling Derek that it accidentally got there. During surgery, he and George discover that it was deliberately put there, and one of the climbers admit that he was trying to "put him out of his misery". Adele is saved after Richard finds her lying in the bathroom and is stabilized, but soon suffers a miscarriage. Richard learns Adele was actually pregnant with his son, not someone she had one night stand with. Bailey is disappointed to see that Callie is the new Chief Resident and begins to question her abilities as a surgeon. Richard chooses Derek as Chief of Surgery, but he refuses, telling him that he isn't done doing what he does best. Cristina and Burke's wedding day arrives, but Cristina won't stay out of the hospital. However, Cristina's nervousness results in Burke's realizing that he does not love the real Cristina and leaves her. Meredith and Derek are uncertain about their future and despite Derek admitting that she is the love of his life, they call their relationship over.