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.
In the first part of the two hour season finale, Izzie spends time with a fellow cancer patient and contemplates whether or not to undergo a risky surgery, as Mark is ready to take his relationship with Lexie to the next level and a patient makes Owen reassess his place at Seattle Grace.
As Meredith, Derek and all of their friends prepare for the big wedding, a group of college students, injured in a car crash as they were heading to their graduation ceremony, is admitted to the ER. Meanwhile, Izzie fears the worst when she begins experiencing familiar symptoms.
As preparations continue for Meredith and Derek's wedding, several residents must face the arrival of their parents at the hospital: Izzie's mother Robbie causes a stir when she pays a surprise visit, and Thatcher returns to make amends with Meredith and Lexie. The Chief clashes with Meredith over a controversial medical case.
Amidst a series of intense treatments, Izzie throws herself into Derek and Meredith's wedding plans, but the stress of her illness takes its toll on Alex - who freezes during surgery just as George begins to excel. Meanwhile: Callie's father arrives at Seattle Grace, but is less than pleased to meet his daughter's girlfriend; Owen seeks help to quell his PTSD outburtsts.
All eyes are 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.
After his fellow surgeons try and fail to bring Derek back to work, Meredith must summon the strength to convince him. Meanwhile the hospital is abuzz as Mark attempts a rare face transplant surgery. Cristina, at last awarded her first solo surgery, is more focused on the needs of her friends, and Izzie does her best to keep her medical condition a secret.
After learning at a deposition that more of his patients have died than survived, Derek decides to quit, even as Meredith refuses to give up on him. Meanwhile Bailey and the Chief continue to bicker over her peds fellowship until Adele steps in to mediate. The interns discover something unsettling on a "patient x," unaware that the charts they're looking at are actually Izzie's.
Derek's confidence is shaken like never before as he faces off with Addison over what course is best for their dying pregnant patient; Cristina calls the abilities of a renown surgeon into question after she botches a standard procedure; and Bailey, who has decided to pursue a fellowship in Pediatrics, is appalled by the Chief's less-than-stellar recommendation letter.
In a "Private Practice" crossover episode, Addison, Naomi and Sam rush Addison's ailing brother, Archer (Grant Show), to Seattle Grace in an effort to save his life. Meanwhile, Owen runs into a significant someone from his past; and Izzie employs her fellow doctors in a medical game designed to help teach the interns.