The fifth-year residents return for the first day of a year that will make or break their careers: Meredith faces the consequences of tampering with Derek's clinical trial and is terminated at the hospital; April tries to step up to the plate as Chief Resident in the wake of a giant sinkhole in the middle of Seattle; and Cristina and Owen are still at odds over their drastically different feelings for their unborn child.
News of Meredith and Derek's unsteady relationship raises a red flag for Zola's adoption counselor; Alex quickly realizes that he has become the outcast of the group after ratting out Meredith; and Cristina makes a tough decision regarding her unexpected pregnancy. Also, Chief Webber brings Henry in for a last minute surgery, alarming Teddy.
The Chief makes a career-changing decision that shocks Seattle Grace Hospital; Cristina and Owen try to find normalcy in their relationship; April continues to struggle in her new role; and the 5th year residents are given their first solo surgeries, only to find out that even the most routine procedures aren't always easy.
The doctors of Seattle Grace are called upon to man up when a stampede at a comic book convention causes an influx of colorful characters in the OR-blurring the lines of fantasy and reality; Mark shows his softer side with baby Sofia when Arizona and Callie go out of town.
The residents try their hardest to impress surgical great Catherine Avery, who also happens to be Jackson's mother, when she arrives at Seattle Grace to perform a groundbreaking transplant surgery.
After being blackballed by most of the surgeons, Meredith uses Lexie to spark Derek's interest in her patient's rare brain tumor case and, in secret, gives guidance to April with Bailey's clinical trial; Callie's wish for Arizona and Mark to form a friendship comes to fruition and she realizes it's more irritating than helpful.
Owen stresses teamwork and moves his leadership role over to the baseball field when he signs the doctors up for a baseball league, pitting them against their biggest competition, Seattle Presbyterian Lexie tries to hide her jealous rage when she sees Mark with a new woman, but her emotions get the better of her Alex fights to keep Zola at Seattle Grace after it is suggested that she be moved to another hospital due to a conflict of interest with Meredith and Derek.
The doctors become nostalgic when George O\'Malley\'s mother, Louise, returns to Seattle Grace for medical help after a botched surgery at a neighboring hospital; the residents are inspired by a medical miracle when they witness a harvested heart that continues to beat outside the body.
Teddy puts her husband\'s life in the hands of her peers when Henry is sent to the OR for surgery and she\'s called away on another case; Meredith and Derek receive the long-awaited news about Zola; Callie and Jackson come under fire when their patient experiences post-surgery complications.
A severe car crash involving an entire family results in an all-hands-on situation in the ER, as the eldest daughter is left to make the toughest decision of her life. Meanwhile Teddy, still in the dark about Henry's death, calls upon Cristina to help with her patient in the O.R., and Lexie finds herself working alongside Mark's new girlfriend, Julia, during an eye surgery.
The doctors split into teams for a risky surgery involving conjoined twins; Bailey recruits Meredith to be a buffer between her and Ben when he puts pressure on moving their relationship to a more serious level; Richard teaches Alex a tough lesson in the OR; meanwhile Teddy questions Cristina about what exactly happened to Henry during his surgery.
Richard performs his 10,000th surgery on a pair of bickering sisters who come into the hospital for a liver transplant; Derek and Lexie take on a neuroblastoma case that has been previously deemed inoperable; Teddy and Cristina cross the line when they go against Owen\'s orders and try to steal a case from Alex and Dr. McQueen.
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?
In the spirit of Valentine's Day, Meredith and Derek try to have a night to themselves when Lexie offers to watch Zola; Callie hands babysitting duties over to Mark so that she can surprise Arizona with a romantic evening; and Ben proves to Bailey that he knows her better than she thinks.
In a final attempt to save Erica's life, Amelia arrives at Seattle Grace to beg Derek for help with the gliosarcoma case; Cristina and Owen engage in heated arguments during marriage counseling; Alex realizes that in order to be a good doctor, he'll need to improve his people skills; and Meredith is given a chance to shine when a man enters the ER after getting his hand stuck in meat grinder. Meanwhile, the residents continue to study for their upcoming oral boards.
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.
Derek asks Meredith to work with him in neuro again; Catherine Avery comes back to Seattle Grace and takes an interest in Richard; Cristina becomes increasingly suspicious of Owen; Morgan may be falling for Alex.
A lion breaks loose in Seattle, leaving a couple's lives and relationship at risk; Lexie overhears Mark's discussion about moving in with Julia; Teddy begins to take steps towards coming to terms with Henry's death; Callie grills Arizona on her past lovers; and Alex requests to be taken off Morgan's preemie case when she becomes too dependent on him. Meanwhile, Meredith tries to be a support for Cristina as the tension between her and Owen hits a boiling point.
A devastated Cristina presses Owen to confess the intimate details of his affair; Mark takes his new authority very seriously when he steps in as chief for the day and butts heads with Richard over a patient's liver transplant; and Callie deems Meredith ready for the boards, while the rest of the residents continue to stress about the exam. Meanwhile, Callie, Arizona and Bailey plan a much needed ladies night for Teddy.
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.
After eight years of practice, the residents head to San Francisco for their oral boards; sparks fly between Catherine and Richard when they bump into each other at the hotel; Bailey intervenes after Owen and Teddy get into a heated argument about their young car crash patient; and Mark tries to recruit Lexie for one of his cases. Meanwhile, Alex feels guilty for being away from the hospital when Tommy's health begins to fail.
The residents agonize over their oral boards, reliving every answer they gave during their exams; Arizona's close childhood friend comes to Seattle Grace for medical help; the doctors work on a patient who is missing one third of his skull; and Julia asks Mark to start a family with her. Meanwhile Catherine tells Richard that one of his residents has failed.
The residents determine their future as they make their final decisions regarding post residency positions; Mark admits to Derek that he is torn between his love for Lexie and the fact that Julia can give him everything he's ever wanted; Ben plans something extra special for Bailey, but she is preoccupied with her work; and Arizona encourages her childhood friend, Nick, to have surgery. Meanwhile a couple on their third honeymoon come to the hospital complaining of mysterious symptoms.
Faced with a life threatening situation, the doctors must fight to stay alive while trying to save the lives of their peers; Bailey and Ben make a decision regarding their relationship; and Teddy is presented with a tempting offer. Meanwhile, Richard plans a special dinner for the residents.