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. Addison treats an infant who is in critical condition after being thrown in the trash on high school grounds, and she must deal with a group of 14-year-old girls and their parents to find out who is the teenage mother. 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, and 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 hosiptal 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 and believes herself to be a superhero. 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.
Derek learns one of Addison's secrets. Bailey talks about motherhood and depression to a mother who is set to have cancer surgery and who seems to not care about any decisions concerning the future. A resident is fiercely questioned about the passing of a male patient. An ex-couple meet before lunch and get stuck - Meredith and Addison work on their case. Things get awkward when the ex-couple's daughter, Michelle, arrives at the hospital.
Cristina gets to scrub in on a rare surgery which incites envy. Alex questions his future in plastics. George and Addison work together with Noelle. Noelle is pregnant with twins but one of them is growing slower than the other. Her fiance has problems of his own. Derek's sister visits. A patient's wife makes things hard on the staff since she has made her husband's health her job. A woman's sexual exploits are questioned.
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.
George's father has a serious heart problem that requires surgery and George chooses Burke to do the procedure. Burke doubts himself because he knows the pressure this kind of surgery will put on him, but Cristina believes the team can handle it. Derek works with Meredith on being a couple again and tries work with Addison on more civil terms. A patient has had mutiple plastic surgeries so that his girlfriend will like him more. A mom wants her daughter's babysitter fired, after she is brought in with multiple injuries, but the girl likes the babysitter more than her mother.
A traumatic car accident fills the ER. Izzie pushes the boundaries of her probation. Cristina has a crisis of conscience about her deceptive teamwork with Burke.
Recent events strain Burke and Cristina's relationship. Mark and Derek must work together when two close-knit brothers seek medical help. One of Meredith's half sisters is admitted to the hospital.
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.
Cristina and Burke continue to play Uncle until one of them gives in. Derek and Meredith are fighting over the reason for their sleepless nights. Meredith tries to talk to her father about his side of the story. There's tension between Alex and Addison. There is even more tension between Addison and Mark. Addison confides in Callie. Bailey wishes she didn't have to keep a secret from one of the interns. Callie rushes to be with George after she learns that his dad needs an emergency procedure. Izzie may have found 'some good to do' with her inheritance.
George has become a sex machine. Dr. Bailey has the idea of opening a free clinic. A doctor at Seattle Grace gets proposed to. Addison is avoiding Alex. The Chief officially announces his intention to retire to the administration of Seattle Grace and to Adele. Rumors of Richard's retirement spread throughout the hospital. Two best friends are left with a difficult decision due to an advanced illness. Derek yells at Meredith.
The chief's announcement of his retirement sparks competition between Derek, Burke, Addison, and Mark. A surgical patient endangers the lives of those surrounding her. Meredith's mother becomes lucid. Cristina and Callie consider marriage proposals. The Denny Duquette Memorial Clinic opens and Izzie cannot wait for the first patient to arrive.
The staff is trying to deal with antsy patients while dealing with a major disaster when a cargo ship strikes a Ferryboat in Seattle. The Chief must choose a team to go out on location and save what is left of the few lives spared.
Almost everyone searches for Meredith while they ponder her place in the world. Addison considers pursuing Alex. Izzie takes desperate measures to manage the situation she is in. Someone ends up on the brink of passing. Cristina and Burke have a blow-up fight about their announcement.
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. Someone else dies.
Alex grows closer to Jane Doe as he continues to work on her case. Helen Crawford flies into Seattle for surgery. She knows someone on the staff. Colin Marlow enters the race for Chief of Surgery. George faces more problems with Callie and Izzie. Callie reveals a big secret. Someone treats a WWII veteran. Also Derek treats a patient near and dear to him.
Callie's father comes to Seattle Grace and meets George, the hospital starts interviewing candidates for the Chief's position, and Alex helps Jane Doe figure out her place in the world. George and Izzie have a few morning-after symptoms.
Colin Marlow continues to try to get in the way of Cristina and Burke's relationship. The daughter that Izzie gave up for adoption needs something from her. This episode features a pro chess player, a flirtatious woman, and a mother named Mrs. Malone. Mr. and Mrs. Malone haven't talked to their daugther in a while because of their son-in-law. Someone goes to see a priest.
The attendings vie to be Chief. Two people who haven't slept together before, will. McSteamy's 60-day vow of chastity has a conclusion. We meet a boss, his assistant, and his wife. We also get to see someone being treated in the clinic. Derek has more questions about his relationship with Meredith. The chairman of the hospital board is admitted as patient. Callie confronts Izzie about her relationship with George.
Meredith works on her relationship with Susan and Thatcher. Cristina has to deal with her mother and Burke's. Alex continues to tend to Jane Doe/Ava. Meredith and Derek's relationship has a problem that needs resolution quick. Addison sees her god-daughter which leads to a job offer outside of Seattle. Derek has to perform surgery. Burke has a reservation about marrying Cristina. Many new people guest star in the course of Addison's road trip to California. Addison considers moving to be closer to her old med school friends until she discovers that drama she wishes to leave behind isn't exclusive to Seattle. Her friends who she thought had it all, are divorced. A pregnant woman must discover who the father of her child is.
Meredith works on her relationship with Susan and Thatcher. Cristina has to deal with her mother and Burke's. Alex continues to tend to Jane Doe/Ava. Meredith and Derek's relationship has a problem that needs resolution quick. Addison sees her god-daughter which leads to a job offer outside of Seattle. Derek has to perform surgery. Burke has a reservation about marrying Cristina. Many new people guest star in the course of Addison's road trip to California. Addison considers moving to be closer to her old med school friends until she discovers that drama she wishes to leave behind isn't exclusive to Seattle. Her friends who she thought had it all, are divorced. A pregnant woman must discover who the father of her child is.
The interns finally take their medical exams, the biggest test of their intern careers, and one of them is ill-prepared. Callie grows more suspicious of George and Izzie. The doctors treat a patient named Dale. Three mountain climbers are treated. Cristina works on her vows. Adele wants Addison to keep a secret from Richard.
Callie and George make a big decision. A successor to Chief Webber is named. A man named Jeff Pope arrives. He is looking for his wife and newborn child. Cristina and Burke's wedding day has arrived and so have the interns exam results.