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.

Derek is still operating when he finds out about Meredith's current situation. Meredith is freaking out about her situation. Webber and Bailey are dealing with medical health issues. Cristina and Izzie have their own issues to deal with because of Meredith's situation. Addison freaks out when George tries to find a solution to Bailey's impromtu postponement. Overall, Seattle Grace Hospital is still under code black and the situation is getting worse.

Denny needs a heart or else. Izzie and George go crazy trying to get him one. Derek has the life of a friend in his hands as he operates on Burke who has been shot. Burke cannot operate on Denny after Denny's heart stopped and now Denny is in a dire condition. Cristina gets put in charge of the ER and she is worried about Burke.

Meredith must make an important choice about which path she wants to follow to determine the future of her love life. While she considers her future she and others have flashbacks of their pasts. Cristina spends time with Burke while he recovers. Webber and Adele have a conversation after he spends the night at the hospital. Everyone attempts to deal with Izzie's choice to quit. George seeks relationship advice from Derek.

After the Chief announces his retirement, rumors begin to circulate on his departure and successor. Mark is determined to leave Seattle for good but Meredith accidentally has him stay after letting him know of the open Chief position. Derek is angry at Meredith for causing Mark to stay in Seattle, but soon realizes that she is not the reason he is really angry. The attending physicians at Seattle Grace Hospital fight to get Richard's attention, but he expresses his disappointment. He also displays his lack of support in Bailey's plan to create a free medical clinic, but she ultimately goes through with her plan when Izzie offers to spend her entire 8.7 million dollar inheritance on the project. George, devastated after his father's death, uses sex to overcome his grief, and eventually proposes to Callie. Cristina and Burke still don't speak to each other, but he breaks the agreement when he proposes to her. Richard endeavors to reunite with his wife, Adele, and decides to retire, only to come home and find his wife with another man.

The interns finally take their first year medical exams, the biggest test of their careers, and one of them is ill-prepared. Callie grows more suspicious of George and Izzie. The doctors treat a patient named Dale. Three mountain climbers are treated. Cristina works on her vows. Adele wants Addison to keep a secret from Richard.

The mountain climbers lie about the axe in their friend's head, telling Derek that it accidentally got there. During surgery, he and George discover that it was deliberately put there, and one of the climbers admit that he was trying to "put him out of his misery". Adele is saved after Richard finds her lying in the bathroom and is stabilized, but soon suffers a miscarriage. Richard learns Adele was actually pregnant with his son, not someone she had one night stand with. Bailey is disappointed to see that Callie is the new Chief Resident and begins to question her abilities as a surgeon. Richard chooses Derek as Chief of Surgery, but he refuses, telling him that he isn't done doing what he does best. Cristina and Burke's wedding day arrives, but Cristina won't stay out of the hospital. However, Cristina's nervousness results in Burke's realizing that he does not love the real Cristina and leaves her. Meredith and Derek are uncertain about their future and despite Derek admitting that she is the love of his life, they call their relationship over.

A face familiar to one of the year-twos shows up and dredges up issues that were never really dealt with. A teen soccer player needs counseling because of his father and surgery for an injury he sustained while playing the game. Another patient's, named Courtney, finds out that her cancer is back.

The clinical trial continues to make progress. The anti-McSteamy club creates new initiatives but that isn't enough to stop one woman from spending time with him. Christina is affected by Burke's career developments.

A couple undergoes surgery. Derek and Meredith's clinical trial gets a second shot from a new patient. Izzie helps Alex. McSteamy hooks up with someone.

Derek decides to quit after learning that more of his patients have died than survived; Izzie's interns make an unsettling discovery about "Patient X."

Owen recruits Dr. Teddy Altman, a former Iraqi veteran, as the new cardiothoracic surgeon. Cristina questions her abilities in the E.R. and relationship with Owen. Izzie returns to Seattle Grace with her high school mentor seeking treatment for his dementia. Richard's responsibilities, post-merger, are taking a toll on him.

Meredith, looking to prove she is Chief Resident material, learns that anything and everything can happen in an hour's time when she steps up to run the ER for a night; meanwhile, Bailey sneaks off with Eli and gets into a little mischief, and everyone is surprised when the Chief's wife, Adele, shows up as one of the ER patients.

Meredith must choose between her fertility treatments and her eyesight when she begins having trouble seeing, Mark makes it clear to Callie and Arizona that he takes his role as father-to-be very seriously, and April discovers there's more to Dr. Stark than first appears.

Richard is desperate for Derek and Meredith to accept Adele into their Alzheimer's trial, but will Adele stand in her own way? Meanwhile Mark and Arizona have conflicting ideas of the kind of baby shower Callie wants, Teddy is freaked out when Henry has another health complication -- leaving them both a little exposed -- and the competitiveness amongst the residents for the Chief Resident position is amplified when Richard receives the green light for his diabetes clinical trial.

Everyone pulls together to help Callie and baby Sofia on their painstaking journeys to recovery in hopes of allowing mother and baby to finally meet; the sudden death of a clinical trial patient has Derek proceeding with more caution while Meredith makes a calculated and risky move; Alex treats a cranky old rich woman dying of cancer and gets an idea for a grandiose endeavor that is sure to get him the Chief Resident spot; and Teddy is pleasantly surprised by the return of a familiar face.

Richard performs a monumental surgery in his career; Derek and Lexie attempt to work miracles for a patient with an inoperable tumor

As Meredith puts Zola to bed and falls asleep, she begins to wonder -- what if her mother had never had Alzheimer's and she'd had loving, supportive parents? The reverberations of a happy Meredith Grey change the world of Seattle Grace as we know it. What if she had never met Derek in that bar and he had never separated from Addison? What if Callie and Owen had become a couple long before she met Arizona? And what if Bailey never evolved from the meek intern she once was?

As Adele's condition continues to deteriorate, Richard considers altering their living situation; an explosion at a local coffee shop results in a busy day in the ER for the doctors; Callie takes Meredith under her wing by helping her study for her boards; Lexie joins Arizona and Alex in peds, as they continue to care for intern Morgan's premature son; and when Jackson snaps at a patient, Mark encourages him to find ways to relieve his stress. Meanwhile, Cristina lets her suspicions get the best of her.

The doctors work on a Jane Doe, who turns out to be the subject of a case that gained national interest; Cristina proves to be the highest in demand as the residents begin their interviews for post-residency positions at prospective hospitals; and Richard is faced with an unsettling realization when he visits Adele at Rose Ridge.

As the rest of the doctors prepare for Bailey's wedding, Richard helps her through a bout of pre-wedding jitters. Meanwhile, Lizzie butts heads with Meredith, and Callie and Jackson try to convince Derek to participate in a risky surgery that could fix his hand.

Bailey puts her wedding day on hold and continues her efforts to save Adele's life, Cristina and Owen remain undecided about their pending divorce, while Arizona and Callie try to get their spark back. Meanwhile, the hospital becomes inundated with a group of bikers after a horrible accident.