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 doctors meet the world's oldest intern. Marcy brings in her son Henry because she finds his change in behavior suspicious. A patient named Connie may lose her vocal chords unless Mark and Richard can perform a radical new surgery. George impresses the other interns at work but at home he is trying to deal with his guilt about having sex with Izzie.

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.

Addison visits Seattle Grace because they need skills that only she has. Rebecca/Ava returns with news for Alex. Meredith and Derek's clinical trial experiences one or two developments.