Addison is not prepared for all the changes that greet her upon her return to Seattle Grace for a specialized surgery, Meredith and Derek begin their clinical trial, Izzie feels left out, and Karev is confronted with an unexpected announcement.
A surgical team battles the clock as they try to save a boy encased in cement, Karev's situation with an ever-disintegrating Ava brings back painful memories that interfere with his judgment, Derek and Meredith have one last chance at their clinical trial.
Meredith and Derek are at odds over whether or not to continue with their 13th clinical trial patient and the doctors lift the final critical pieces of cement from the young boy's body. Meanwhile, Alex rushes Ava into the hospital and is forced to confront the reality of her condition.
Meredith and Derek find that "happily ever after" isn't as easy as they hoped, Cristina finds interest in a military doctor, and the Chief is surprised to hear that Seattle Grace is no longer ranked as a top-tier teaching hospital.
As a group of best friends deal with the aftermath of their car crash, Dr. Torres takes the lead on a groundbreaking course of treatment for one of the patients. Meanwhile, Major Hunt starts to irritate other attendings with his presence in the hospital.
Determined to reverse Seattle Grace's slide into mediocrity, the chief lays down some new rules for interns and residents with which no one's happy. Derek asks Meredith for further changes in her living arrangements. Lexie challenges Cristina's diagnosis for a patient with a persistent headache, and the chief's preoccupation with reputation blinds him to problems with the physical plant.
Bailey's dream of a domino surgery is scuppered when one of the donors learns of her husband's affair, and Meredith is insulted when she gets no credit for the procedure she and Derek worked on together.