There's tension between Meredith and Addison. We find out why Derek and Addison aren't together. Bailey puts George on an impossible case. The rest of the interns operate on a family that was just in a car accident.

The holiday season has started but not everyone is in a festive mood. This is Alex's last day in the hospital unless he passes his boards practical exam the next day, thus everyone helps him to review so that he succeeds. However, Izzie is not happy about the others helping him and Meredith has to remind her of the true spirit of the Christmas holiday. Justin is in need of a new heart. One is available but he does not want it because he does not believe Santa gave it to him as his mother said. Cristina and Burke, both handling Justin's case, have opposing views on the matter due to their different stances on religion. Despite a reconciliation with his wife, Derek isn't in a festive mood. George has a simple case of a woman who has a bleeding ulcer, he realizes that the ulcer is caused by her entourage but fails to keep them away, with the consequence that it perforates.

A mass trauma situation, which turns out to be a ferryboat accident, challenges the whole staff of Seattle Grace Hospital. Richard finds difficulty in coping with his separation from his wife and dyes his hair "for the ladies", which becomes an internal joke between Mark, Burke and Derek. Cristina tries to tell Meredith about her upcoming marriage, but doesn't have the strength to. George promises to find a woman's son, who has been separated from her at the accident. The woman refuses to go into surgery until she is assured that her son is alive. Izzie has to take care of a man who got stuck between two cars on the ferry, but nobody helps her due to the large number of injured people. Alex rescues a pregnant woman with severe wounds on her face, and promises to take care of her. Meredith looks after a girl who has been separated from her mother after the accident, but accidentally falls into the water and drowns, with nobody but the little girl as a witness.

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.

A patient comes to the ER with a dream and a condition which may prevent him form realizing it. Two patients are competing to win something big. One of them convinces an intern to take their place.

In the second part of the two hour season finale, George delivers stunning news to Bailey, sending shockwaves throughout the hospital, and Izzie's friends anxiously await her recovery from surgery. Meanwhile Bailey is surprisingly displeased after being accepted into the pediatric fellowship program, and the victim of a near-fatal traffic accident brings the talents of Seattle Grace's doctors together. This is the second hour of a 2-hour season finale.

The fifth-year residents return for the first day of a year that will make or break their careers: Meredith faces the consequences of tampering with Derek's clinical trial and is terminated at the hospital; April tries to step up to the plate as Chief Resident in the wake of a giant sinkhole in the middle of Seattle; and Cristina and Owen are still at odds over their drastically different feelings for their unborn child.

As the hospital continues to make positive changes under the new management, the doctors begin to realize that owning a hospital comes with its own set of problems and responsibilities. Meanwhile, Meredith worries about the wellbeing of her unborn baby, Callie and Arizona try to get the spark back in their relationship, and Alex gives Jo‘s new boyfriend a run for his money.

A gas tanker explodes on a Seattle highway, causing multiple injuries, including paramedic Matthew. Meredith and Jo help a frantic mother whose child is suffering from a mysterious illness. Owen bonds with a young boy whose parents are in critical condition. Meanwhile true colors are revealed when Alex is forced to work with Jo's boyfriend on an ailing patient.

The doctors of Grey Sloan Memorial Hospital are forced to put their emotions aside when a catastrophic event occurs.

One of Grey Sloan Memorial’s own is seriously injured, making the team reflect on what is truly important to them. Meanwhile, Nicole Herman pays a visit to Grey Sloan and talks to Arizona about an exciting opportunity.