Tensions are running high at Seattle Grace with all eyes on Derek as he is set to perform his first surgery after his breakdown; attention is also set on Izzie, whose medical condition requires her to undergo a difficult surgery; and Owen has another PTSD episode that injures Cristina and traumatizes both of them, throwing the future of their relationship into question.

As preparations continue for Meredith and Derek's wedding, Izzie receives a surprise hospital visit from her handful-of-a-mother, Robbie. Meanwhile, a newly sober Thatcher visits his daughters, Meredith and Lexie, in order to make amends, and the Chief and Meredith bitterly fight over a controversial medical case.