While off from work, Meredith and Cristina discuss their mutual man problems and are interrupted when Joe, the bartender, collapses. While Webber recovers from his surgery, he appoints one of the surgeons as interim chief, but has George report to him all the happenings at the hospital. While Meredith learns more about Derek and Addison's past relationship, Cristina tries to decide what to do in her relationship with Burke.

A family arrives at Seattle Grace after a car accident. While treating the members of the family, Alex discovers that their problems are deeper than their injuries. Meanwhile, Mrs. Webber admits her marital worries to Richard as he recovers.

Meredith's secrets about the state of her mother, Ellis Grey, are revealed to the staff when Ellis is brought in for surgery. Meanwhile, secrets about Cristina's health are also revealed.

While trying to recover, Cristina proves to be a difficult patient, and matters are made worse when her mother visits. Ellis Grey, Meredith's mother also proves to be a difficult patient when she has the staff running in circles to please her. Derek and Meredith's relationship remains in limbo when Addison's departure is postponed when she becomes involved with the treatment of a cystic fibrosis patient.

Meredith and Derek have to use more than their medical knowledge when a woman's strictly religious father forbids her from having an operation that would save her life. Meanwhile, George and Alex are forced to perform a surgery in scarce conditions, and Derek is forced to decide between Addison and Meredith.

Meredith temporarily forgets her worries about Derek's decision when a train crash results in dozens of injuries. Later, Addison sees potential in Izzie, but Izzie is forced to choose between her friendship with Meredith or her career.

The entire staff is in awe when a patient, Shane, comes in with a hysterical pregnancy while Cristina, Izzie and Meredith aggressively work on his unique case. Meanwhile, Alex is encouraged to show his feelings for Izzie after treating a young, sheltered young patient.

Friends of Derek and Addison come to Seattle Grace for preemptive surgery to avoid breast and ovarian cancer. But the arrival of their friends tests Derek and Addison's professional relationship. Meanwhile, George treats a patient who fell five stories and is dissatisfied with his outcome and Cristina and Burke attempt a normal date.

Thanksgiving proves to be a difficult holiday for both the interns and residents. Izzie plans a big dinner, but it doesn't look like all the invited guests will show up. Meanwhile, George participates in the O'Malley turkey hunting tradition, which abruptly ends after a shooting accident and Meredith treats a comatose patient whose condition might be better than it appears.

Meredith is horrified when her one-night stand needs treatment after suffering from priapism. Meanwhile, Alex begins to frustrate Izzie and a pregnant woman carrying quintuplets stresses over her high-risk pregnancy.

Cristina finds little sympathy for an inmate who purposely endangers her health to get out of serving her term in solitary confinement. Meanwhile, the interns are put in charge of watching the newborn quintuplets, each with varying health concerns; Izzie's frustrations with Alex's shortcomings hit their end; and Derek teaches Izzie an important, yet painful lesson.

Burke and Cristina's differences are shown when a young boy needs a transplant but he refuses to get it. Meanwhile, the interns help Alex prepare for his exams when it's revealed that he failed them. Meredith has to re-instill the Christmas spirit in Izzie and Derek refuses to feel festive.

As the new year unfolds, Izzie vows to let Alex's affair go, and it comes easier when she hits it off with Denny Duquette, a heart transplant patient. George treats Bex, a teen hermaphrodite, with a tumor and Alex treats a man who ate his novel after not being pleased with the results. Meanwhile, Derek talks with Meredith's mom, Addison expresses her disgust with Derek's living arrangements, and the residents, especially Cristina, have a hard time dealing with the new work limit.

Cristina and Meredith hide the truth about their relationships from each other. George is assigned to discharge an elderly patient who refuses to leave; and Alex learns the fate of his career when the results from his medical exams come in.

When the nurses at Seattle Grace go on strike, the doctors are forced to work without them. While most of the doctors cross the picket line, George refuses to cross due to his union roots. With Bailey on maternity leave, the interns meet their temporary resident, Dr. Sydney Heron, who is the exact opposite of Dr. Bailey, which Cristina has a hard time adjusting to. Meanwhile, secrets from Izzie's past are revealed as she treats a young, pregnant teen; and Meredith makes a mistake in treating an elderly patient.

All morning, Meredith felt like she was in for a bad day. Her fears are realized when a medical case threatens the lives of everyone at Seattle Grace, causing officials to put the hospital on a code black.

Despite the staff doing all they can, the potentially disastrous situation continues to escalate. Meredith begins to panic about her situation, as does Derek when he's told about her circumstances. Meanwhile, while the hospital is in chaos, Bailey and Webber have to deal with their own health issues.

When a person from Derek and Addison's past arrives at Seattle Grace, their now stable relationship is shaken up. Meanwhile, after visiting with her mother, Burke is told Cristina's secret; and after a visit with her mother, Meredith digs to find the family's secrets.

Meredith and George fight over who gets to treat a patient. Bailey, despite being on maternity leave, treats Addison for a specific feminine problem. Izzie starts spending time with Denny, and Alex becomes jealous. Meanwhile, Burke treats a man who had a heart attack, and the man's fiancA©e leaves him when she learns about the risky surgery he's decided to have.

Cristina has a hard day on the job when Bailey has her take care of her baby after she gets involved in a case, despite being on maternity leave. Meredith continues to deal with the fact that she slept with George, who begins to bond with Burke much to Cristina's disgust. Addison and Derek have a deep talk about their relationship and Denny continues to get in the way of Alex being closer to Izzie. Meanwhile, the interns must deal with a hockey player who wants an unnecessary amputation and a woman with a fork stuck in her neck.

The doctors' superstitious sides are brought out after several deaths and strange events take place at Seattle Grace. Derek and Addison talk about a more permanent living situation, Izzie worries about Denny's surgery, and Richard gets reacquainted with an old friend.

Derek performs brain surgery on Andrew, a young spelling bee champion who suffered a serious head injury. George, who begins to overstay is welcome at Burke's, has trouble not speaking up when one of his patients constantly lies about her health to her daughter. Bailey begins to worry that the interns will no longer see her as the Nazi now that she has a child. Meanwhile, Addison treats a patient with pregnancy issues; Alex gets a lesson in manners; and secrets are revealed about Meredith's father.

A strict Catholic mother of seven children comes to the hospital to ask Addison for medical help because her equally religious husband refuses to use condoms. Addison is able to come up with a solution to her problem, but Alex's interference causes problems for both Addison and the mother. Derek rethinks his marriage after treating a divorce attorney for seizures. Izzie hounds George for information about his private life and pressures him to move back into the house. Meanwhile, Meredith agrees to go out with Doc's vet and Burke is faced with considerable pressure when he has to operate on his musical hero.

The interns attend to Marshall, an intern from another hospital with short-term memory loss. Marshall was also the cause of a bad accident involving a family, which leads Derek to let his emotions get in the way of his work. Meanwhile, a woman from the past comes to visit one of the female interns, and Burke and Izzie have an idea relating to Denny's condition.

Finn continues to work with Doc and is able to give his owners, Meredith and Derek, and update on his condition. George is assigned to work with Derek, while Meredith is assigned to work with Callie. Denny still is without a heart donor, leaving Izzie and Burke to continue the hunt for a potential donor. Meanwhile, a 12-week pregnant woman dies in the O.R., and her parents' decision to try to keep the baby alive creates a rift between Addison and Derek.

George and Izzie race to find Denny a heart as his heart gets weaker and weaker by the minute. Derek is faced with the pressure of performing surgery on one of his friends, while Cristina is faced with the pressure of running the O.R. after she is left in charge. Meanwhile, the interns are supervised by Erica, a new attending, who tries her hardest to act like Bailey, but has a tough time doing so.

After Richard learns who Derek is operating on, he tries to pump Addison for information. Callie and George have a talk about their relationship and George's true feelings. Meanwhile, Meredith and Derek get together to talk about Doc, and later realize that their feelings for each other may not entirely be gone despite Finn being in Meredith's life and Addison being in Derek's.