The nurses are on strike and everyone is suffering. Bailey is on bedrest, meaning the interns are being overseen by a new resident, Sydney—the anti Bailey. All the interns find a way to avoid this ever chirpy cheerleader of a surgeon, except for Alex and Cristina, who wind up working with her on a case of flesh eating bacteria on her leg. Alex and the resident try to save the patient's leg, where Cristina sees amputation as the only way to save the girl's life. She even goes to Burke for help, having his question the resident's methods in the OR while she operates on the leg. Cristina winds up wrong and Burke isn't very happy that he overstepped his bounds as a doctor because of his role as her boyfriend. Izzie on a case with Addison with a pregnant teenager who's baby needs an EXIT surgery—a risky operation that requires half delivering the baby before operating and then finishing the delivery. The girl, though, is not sure of her ability to be a mom so young, to which Izzie makes a startling revelation: she had a daughter when she was 16 that she put up for adoption.
George doesn't have a case in this episode because he's siding with the nurses while they are on strike. George refuses to cross the picket line into the hospital until the nurses themselves talk George into going in there to at least check on their patients. Meredith saves a dying elderly patient who was DNR, but not properly labeled as such. Alive only in the loosest sense of the word, the patient's friends want Meredith to take out the tube keeping her alive. Meredith has end this life, which causes her to have a mini breakdown in the closet at she thinks about her own mother's mortality (and that fact that she seems to be alone). Derek is there to comfort her. Though initially disapproving of the fact that Richard had been secretly visiting her mother, Meredith decides to let him continue doing it because he's like Ellis's lifeline that she doesn't want to pull out.