Entering their first year as residents, Meredith Grey, Cristina Yang, Izzie Stevens and Alex Karev now have interns of their own to mentor. Among the new interns are George, forced to repeat his internship after failing his exams, and Lexie Grey, Meredith's half-sister. Another two new interns will be introduced in this season premiere. And they'll have their hands full when a three-car accident sends multiple casualties pouring into Seattle Grace. Some of the doctors need to deal with new stressed out interns. A young boy brings his bleeding deer to the hospital in the hope a doctor will save her.

The doctors meet the world's oldest intern. Marcy brings in her son Henry because she finds his change in behavior suspicious. A patient named Connie may lose her vocal chords unless Mark and Richard can perform a radical new surgery. George impresses the other interns at work but at home he is trying to deal with his guilt about having sex with Izzie.

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.

There has been a bus crash and the patients are in the ER. Meredith and Derek's relationship gets more complicated when he dates a fellow doctor. Meredith's dad goes to visit her at the hospital.

Addison visits Seattle Grace because they need skills that only she has. Rebecca/Ava returns with news for Alex. Meredith and Derek's clinical trial experiences one or two 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.

As Meredith and Derek begin to find that their "happily ever after" is anything but easy, Cristina develops a crush on a military doctor who brings in a trauma patient. Meanwhile, the Chief and his staff cope with the news that Seattle Grace is no longer considered a top-tier teaching hospital.

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.

Meredith is sent into a state of panic when Derek finds her mother's diary in the house. Meanwhile, Callie stresses while preparing for her first date with Erica. Later, Cristina stumbles across a part of the hospital no one has ever seen before.

Bailey heads up a "domino procedure" in which each surgery hinges on the one preceding it. Meanwhile, Derek gets sole credit for the brain-tumor study he did with Meredith; Lexie tries to get George to notice her romantically; and Sloan counsels a desperate Callie in the ways of love.

The chief gives Bailey new power and responsibility. He also gives her a very difficult surgical assignment: remove a girl's inoperable tumor. Meanwhile, new trauma chief Owen (Kevin McKidd) challenges the attendings' methods and the residents' skills.

One of Meredith's oldest friends, Sadie, becomes an intern at Seattle Grace, but Mer's friends are less-than-welcoming to her.

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.

Bailey teams with Seattle Grace's new pediatric surgeon, Dr. Arizona Robbins, to save the life of a young patient near and dear to her heart, as the admittance of a death row inmate at the hospital stirs anger in Derek and further erodes Meredith and Cristina's friendship; meanwhile, Callie and Sloan work as a team to fight their respective attractions to Sadie and Lexie, and Izzie tells Alex that she's seeing Denny.

Derek's mother, Carolyn, makes a surprise visit to Seattle and meets Meredith for the first time, as Mark tries to conceal his relationship with Lexie from her as well; meanwhile, death row inmate William wishes to donate his organs to Bailey and Arizona's patient, as Owen and Cristina try to go on their first date.

Bailey grows desperate as a patient's condition becomes more and more dire. Everyone in the hospital is stepping up to try to find the boy a new organ donor, including Meredith, who considers a death row patient's wish to die before execution. Meanwhile, an injury leaves Mark in a compromising position in the OR and Cristina awkwardly avoids Owen.

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

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.

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."

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.

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.

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.

The hospital staff is left to deal with the aftermath of George's passing. Hitting the staff hard, they all find unique ways to get through the various stages of grief. George's mom returns, faced with the difficult task of deciding what to do with his organs.

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.

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.