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.

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.

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.

The men of Seattle Grace go on a camping trip together, Addison and Callie must team up to work on a patient, Meredith assists Sloan with a procedure unlike any she has experienced, and, suspicious of her recent actions at the hospital, Bailey confronts Cristina. A 9-year-old is seen by Cristina after he swallowed Monopoly game pieces. A pregnant 25-year-old, is brought in after she slipped in the shower. She doesn't want medicine to take away the pain from her injury so not to put her baby's growth in jeopardy. Doctors take care of Daniel, a man who wants a sexual reassignment surgery and who now goes under the name Donna. Accompanying Daniel is his wife of the past 10 years, who was surprised to see him want that surgery but, after much struggling, decided to stay by his side.

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.