Meredith and Izzie take up knitting. Derek operates on Andrew, a spelling bee champ with a serious head injury. Bailey gets in on Andrew's surgery because she's worried that her coworkers won't recognize her Nazi-status now that she's a mother. Addison's patient has an unborn baby with medical issues. After Alex fails to bite his tongue when a terminal patient routinely lies to her daughter about her health he gets a lesson in bedside manners from Burke. George also begins to overstay his welcome at Burke's apartment after Callie visits him. Meredith has more confusing and uncomfortable encounters with members of her family. One of the female doctors meets a veterinarian named Finn. Izzie flirts with Denny and they play more naughty-Scrabble. Meredith, Derek, and Addison sarcastically take another small stab at their friendships.

Addison's patient is a Catholic mother of seven. Addison gets in trouble after learning that the patient's husband won't use contraceptives. Derek treats a divorce attorney who asks if Derek is in need of her services. While Izzie and George are talking about their personal lives they "overhear" part of Derek's conversation with the divorce attorney who calls herself one of Seattle's best. Alex gets in trouble with Addison yet again for not being able to keep his mouth shut when other people think he should. A legendary jazz musician refuses to see medical reason. The musician is Burke's musical hero. Finn makes Meredith breakfast.

The staff attends to an intern from another hospital who has short-term memory loss. This intern, named Marshall, also has caused a car accident that involved a married couple, their unborn baby and the woman's parents who the staff are also treating. The pregnant woman is named Melanie and she will die but her baby may survive. One of the female interns meets up with a woman from her past who is planning on having a family of her own. Cristina is in a good mood although Alex, Izzie, George, and Meredith are having problems but in the meantime Burke hasn't forgiven Cristina for her late night faux pas. Meredith and Izzie are making fun of Callie's household habits and George and Callie are having a fight because of George's roommates. Addison is continuing to own Alex and he's upset about it. Denny has an outburst at Izzie and Derek has an outburst at Meredith.

George and Derek work together, Denny still doesn't have a heart, and Meredith gets paired with Callie. A 12-week pregnant girl dies in the O.R. and her parents try to keep the baby alive. This causes tension between Derek and Addison. One doctor's overreaction unites two bickering patients. Finn is still treating Doc for medical problems.

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.

Cristina meets Burke's parents, the interns try to get Izzie's job back, and Addison takes a day off, a surgical patient may be living her last day. Some of the interns want to know why Bailey won't talk to Izzie. Meredith tries to decide between Derek and Finn and comes to a decision somewhat. Webber finds out that Callie has been living in the hospital and he confronts her about it.

The staff tries to prevent a patient from getting an elective surgery. Cristina tries to help Preston cope with the after effects of his surgery. A patient bails on their surgery. Someone goes to a bed-and breakfast. Alex deals with a patient who has had a high amount of injuries in the past. A man undergoes surgery. Before the surgery his wife was only somewhat supportive, but the results may be too much for her to handle. Izzie tries to go back to the hospital for the first time since Denny died. One child's constant visits are noted by a nurse. Two foster patients are met with suspicions of child abuse. George and Callie's relationship moves forward.

Shawn Sullivan, a car salesman who just had surgery, wants to get back to his routine so he doesn't lose his renown. Addison works with a pregnant woman named Rebecca who may need a C-section and Addison doubts her medical skills. Rebecca wants to have the baby naturally. Derek and Mark's opinions clash when the try to decide the course of treatment for a burn victim. Izzie gets surprised. Cristina pushes Burke to get better faster.