Meredith and Cristina lie to each other and themselves about their relationships with McDreamy and Burke, respectively. George is given a hard task to expel a discharged and defiant woman from the hospital. Alex learns his fate after re-taking his medical exams. At the same time Izzie is trying to stop Alex from making stupid decisions when a patient that doesn't speak English is lied to by her coach. George, Cristina, and Alex compete in a hot dog eating competition.

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.

Derek learns one of Addison's secrets. Bailey talks about motherhood and depression to a mother who is set to have cancer surgery and who seems to not care about any decisions concerning the future. A resident is fiercely questioned about the death of a male patient. An ex-couple meet before lunch and get stuck - Meredith and Addison work on their case. Things get awkward when the ex-couple's daughter, Michelle, arrives at the hospital.

The race for the Chief's position is on, and the attending physicians, Derek, Burke, Addison and Mark, compete for Richard's affections by trying to help out everywhere possible. The Denny Duquette Memorial Clinic is open for business, but only one single patient shows up. Izzie is disappointed in what she invested Denny's legacy in, and tries to steal patients from the emergency room. Callie and George get back from Las Vegas, announcing their marriage, much to everyone's disbelief. Izzie is not supportive of their marriage and tries to get George to realize the mistake he has made. Meanwhile, Meredith's Alzheimer's-stricken mother, Ellis Grey, experiences a change in her medical condition by becoming lucid for the day. She is disappointed in the mediocrity her daughter has fallen into and begins to despise Derek, blaming him for what happened to the Meredith that used to be "a force of nature". Ellis has to have heart surgery and, despite her wishes, Meredith schedules her upcoming surgery. Richard talks to Ellis and realizes that she is still in love with him, but loses her memory after their talk ends, before Meredith has the chance to tell her how she really feels.

Izzie and George's new-founded relationship results in them having bad sex. Callie's Chief Resident position is taken away from her, and Bailey is the humble replacement. Meredith can barely handle it with Lexie anymore.

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.

Meredith, Cristina and Bailey come to Lexie and Sadie's rescue when a routine surgery goes horribly wrong, as Owen and Derek treat a man seriously injured while sleepwalking and Mark comforts the sleepwalker's distraught daughter.

Addison, Naomi and Sam rush the ailing Archer to Seattle Grace and reunite with old friends Derek and Mark to help save his life; meanwhile, Izzie employs her fellow doctors in a medical game designed to help teach the interns, and Owen runs into a significant someone from his past

Several weeks after her near-death experience, a recovering Izzie returns to work. Meanwhile, nervous that there will be layoffs in the hospital in the wake of an announcement from the Chief, the Seattle Grace residents compete to survive the cuts, including Cristina, who attempts to work alongside Arizona in pediatrics. And Bailey and Alex's patient's already complex case is further complicated by her schizophrenic son.

After learning of Richard's drinking problem, Derek confronts him for the sake of his friend and the hospital, Izzie returns, hoping to reconcile with Alex, and tensions run high between Teddy, Cristina and Owen in the aftermath of Cristina's startling confession.

When Teddy's patient seeks to end treatment and her life, she turns to Hunt for help. The situation triggers Hunt's memories of his life at war and his past relationship with Teddy. Meanwhile, Callie and Arizona have a difference in opinion on what their future holds, and Richard tries to adjust to his role as a surgeon.

Derek takes Cristina out on a fishing trip; Teddy tries to help a patient who lacks the proper insurance to seek medical treatment.

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.

Meredith, Derek, Cristina and Arizona receive big news regarding the plane crash lawsuit, Richard avoids Catherine's romantic advances and Jackson takes on one of Mark Sloan's old patients. Meanwhile, Derek begins recovery on his hand.

The Grey Sloan Memorial Hospital doctors are faced with the devastation left by the storm. A giant mudslide in Seattle injures a group of first responders and citizens, causing the already short handed ER to spring into action. Meanwhile, Meredith is faced with a tough decision that will affect the life of a loved one, Callie is rocked by the reality of Arizona’s infidelity, and Richard’s life is in extreme danger.

Arizona has a bad day which escalates when she advises one of Callie's patients on a potential double amputation. Derek goes back on a promise to Callie, and Jo and Stephanie come across an abandoned baby outside the hospital. Meanwhile, the doctors deal with the repercussions of the non-fraternization rule, which include meetings with HR and one doctor's suspension.

Cristina won't let herself get excited when she is nominated for a Harper Avery award; Alex thinks about making a change; Callie and Derek work with a machine that recognizes emotions.

Cristina considers her future at the hospital; Amelia and Derek collaborate on a tough surgery involving conjoined twins; Jo takes on too many cases at once; Stephanie stumbles on the truth about Bailey's case.