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.

All the nurses at Seattle Grace Hospital go on strike, leaving the doctors to fend for themselves. George refuses to cross the picket line and finally joins the nurses on their strike while Alex, Cristina, Izzie and Meredith meets Bailey's stand-in: Dr. Cindy Aaron, the complete opposite of Miranda Bailey. Izzie agrees to work on a difficult pregnancy case with Addison, while Cristina and Alex are in the pit attending to a young married woman with a real bad case of rash. Meredith happens on an old woman that she needs to intubate and then learns she was DNR.

After a series of deaths at the hospital some of the staff become very superstitious. Izzie worries about Denny and gets confronted by Alex. A patient with OCD drives Cristina crazy. Derek and Addison discuss their relationships with Meredith. Richard treats a friend from 17 years ago who reveals a secret about a dark time in his past that involves Ellis. George gets an earful about the women he's not talking to. Burke and Cristina argue about kicking George out.

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.

A traumatic car accident fills the ER. Izzie pushes the boundaries of her probation. Cristina has a crisis of conscience about her deceptive teamwork with Burke.

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.

Meredith is still underwater, but nobody seems to notice. Her worsening condition makes her rescuing an urgent matter. Derek finds her coat on a man she had helped, and starts looking for her and, much to his shock, the little girl Meredith took care of suggests that she is in the water. Derek saves her, but she is almost dead, due to hypothermia. Izzie has to perform brain surgery on a man stuck between cars, as he begins to experience seizures. She drills holes into his head, perforates his skull and ultimately saves his life before he is rescued and transferred to Seattle Grace Hospital. George lies to the woman whose son he had been looking for, in order to get to surgery, but still doesn't have any luck in locating him. Alex finds no hope in searching for the pregnant Jane Doe's family as she undergoes surgery. The interns find out about Meredith's situation and express their hopelessness. She wakes up in what appears to be limbo and meets her deceased acquaintances.

Colin Marlow continues to try to get in the way of Cristina and Burke's relationship. The daughter that Izzie gave up for adoption needs something from her. This episode features a pro chess player, a flirtatious woman, and a mother named Mrs. Malone. Mr. and Mrs. Malone haven't talked to their daugther in a while because of their son-in-law. Someone goes to see a priest.

Meredith works furiously to save a paramedic trapped in an ambulance; Lexie holds the life of a patient in her hands; Derek must rely on a nurse to save a patient; Bailey struggles to balance her personal life with her work.

When the plumbing springs a leak, chaos breaks out at Seattle Grace as the Chief tries to put in place new teaching methods. Meanwhile, George takes his residency exam; and Derek attempts to get Meredith's roommates to move out, much to their surprise.

Now that Derek has the engagement ring, he searches for the perfect way to propose to Meredith, as Lexie demands that Mark go public with their relationship, and Bailey, encouraged by her work on recent cases and by Dr. Dixon, considers a new direction for her medical career.

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

Everyone is struggling after losing one of their own and are turning to any distraction they can find. Meredith and Derek seem to be consummating their marriage anywhere and everywhere, while Cristina and Owen have been instructed to abstain from sex by Dr. Wyatt.

As Thanksgiving, Christmas and New Year's pass, Miranda gets a visit from her father, William who disapproves of her choices in life. Mark and Lexie cope with an arrival of a woman from his past. Thatcher questions the Chief's recent behavior as Meredith comes to his defense.

As Derek begins his role as interim chief, he faces a potential lawsuit when Bailey and Meredith's patient awakens from anesthesia mid-surgery. Meanwhile, Teddy refuses to place Cristina on her service, as Arizona tests Alex out in Pediatrics, and Mark refuses to speak to a heartbroken Lexie.