Derek and Meredith try (unsuccessfully) to be discreet as they spend the night together at Meredith's house, but their haggard appearance speaks volumes to everyone - including Bailey, who warns Meredith to end the relationship. Meanwhile George suspects an anesthesiologist of drinking on the job but is reluctant to speak up about it, Alex treats a former competitor who now finds honor in self-mutilation, Izzie has to deal with a patient who won't let go of his girlfriend - literally, and Cristina seems to be battling a case of the flu.

Meredith grows increasingly dissatisfied with the unknown details of Derek's life. Meanwhile, Alex treats Devo, a patient whose religious beliefs jeopardize her chances for recovery; Izzie contemplates reconnecting with her estranged mother; Zoey, a pregnant woman in her 40s who's been diagnosed with cancer, disagrees with Cristina's medical advice; and the interns are mystified by Cable, a patient who's being treated for seizures and who thinks he's psychic.

A sexually transmitted disease breaks out and affects several members of the hospital staff. Chief Webber promptly calls a meeting. Meanwhile, the chief reluctantly tells Dr. Derek Shepherd about his own medical concerns. Izzie and Cristina worry about a patient's wife and daughter who can't agree on his care. Burke treats his college buddy Bill, whose medical diagnosis raises some questions regarding his wife's actions. Then just as Meredith and Derek grow more intimate, a surprise is revealed.

There's tension between Meredith and Addison. We find out why Derek and Addison aren't together. Bailey puts George on an impossible case. The rest of the interns operate on a family that was just in a car accident.

It's Thanksgiving at Seattle Grace Hospital but the holiday's festivites are less than in order. Meredith and Derek try to counsel a family after their relative has had a seriously traumatic accident.

Dorie Russell is waiting for quintuplets, all 5 girls. Her husband seems more concerned than she is but she is set to bring her babies to their term of 36 weeks. All the departments are on call for the quintuplets as three of them have developped problems of different kinds. Meredith last night's stand shows up at the hospital with priapism and they need to call Derek Sheperd for a consult which puts Meredith in a very embarassing position. Alex and Derek must take care of a patient who has a tumor inducing thirst as a side effect. On the love side, Alex and Izzie are having some slight sexual problems, while Meredith goes on adding one night stands and Cristina is thrown off course by being "keyed."

Cristina Yang has little sympathy for Constance Ferguson (special guest star Rosanna Arquette), a prison inmate who jeopardizes her health just to get out of solitary confinement. Meanwhile the interns all keep careful watch on the family of premature quintuplets with a variety of serious health challenges, Izzie's anger at Alex reaches boiling point, and Dr. Addison Shepherd decides to teach Izzie a very painful lesson.

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.

An explosive case arrives at the O.R. that might endanger all the lives of the people working there, which leads Dr. Burke to declare a "Code Black" for the hospital. Bailey worries where her husband is as she is in labor. Also Izzie and Alex may be creating some heat.

Meredith and George are experiencing morning-after tension at home and at work and it has the rest of the doctors wondering what's up. Derek and Addison are experiencing their own version of morning-after tension as a result of Mark's visit to Seattle. Bailey, returning the favor that was done for her during the Code Black situation, must treat Addison for a specific feminine problem. Izzie and Alex are making headway in their relationship until Denny Duquette comes back. Soon Alex is not-so-oddly jealous of the attention Izzie is showing to Denny. Someone finds comfort in confiding in a patient who is going through an ordeal of his own. Burke deals with a patient and gets to observe the patient's unstable relationship with his fiancée.

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.

This episode is the second part of a two-hour season finale. Richard tries to get information from Addison about a family member's condition. Callie and George have a talk about his feelings. Meredith and Derek have a talk about Doc.

Meredith must make an important choice about which path she wants to follow to determine the future of her love life. While she considers her future she and others have flashbacks of their pasts. Cristina spends time with Burke while he recovers. Webber and Adele have a conversation after he spends the night at the hospital. Everyone attempts to deal with Izzie's choice to quit. George seeks relationship advice from Derek.

Meredith discovers that Derek has a problem sleeping while her father comes to visit the hospital. George's father is moving from one surgery to another. A patient named Heather checks into the hospital. Heather is 17 and has a nasty attitude that results from her medical condition and all the surgeries it has required her to have. Izzie has an emotional breakdown when she tries to hand over something very important to her. George's family comes to visit to celebrate his father's surgery. Cristina and Burke are playing Uncle.

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.

Everyone is pushing for Meredith to survive, or in this case to be revived. People are still dealing with the fallout from the ferry disaster. A young man named Lucas is having problems with brain-mouth coordination. Someone else dies.

It's Halloween at Seattle Grace! There may be jokes, pranks, and/or scare tactics. Some of the women form a club based on an experience they all share. A man volunteers for what most of the doctors believe is an unnecessary surgery. One of the patients is in the hospital because they tried to carve a pumpkin in an unconventional manner.

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.

The hospital brings in crisis management to help them sort out allegations against Harper Avery. Nurse Olivia shows up at Grey Sloan with her son, throwing Alex and Jo for a loop Arizona decides to spend more time with Sofia who is having a hard time at school.