The season featured 10 actors credited in a starring capacity. All of the first season cast members returned and were credited for the full season. Kate Walsh, who guest starred in the first season finale, joined the main cast in the series' seventh episode after appearing under a 'Special Guest Star' credit for the first six episodes.
Plot:Addison's arrival in Seattle stirs trouble for Derek and Meredith and, much to Meredith's discomfort, Addison requests her as the intern for her TTS case. Cristina tells Meredith about her pregnancy, but doubts whether she would reveal the truth to the new interim cheif Burke. Richard recruits George to be his eyes and ears around the hospital as he recovers and Izzie sees a new side of Alex.
Episode number: 03
Original air date: October 9, 2005
Plot:Meredith struggles to cope when her mother Ellis is admitted to the hospital and her secrets are made public while Cristina wrestles with whether to tell Burke about the pregnancy until tragedy strikes her during surgery. Izzie tries to persaude Alex to change his ways around the other interns after seeing the softer side of him. Addison makes it clear to Derek that she wants to fight for their marriage and Richard faces his past when he learns of Ellis' Alzheimers.
Episode number: 04
Original air date: October 16, 2005
Plot:Addison presents Derek with divorce papers but once the end of his marriage is in sight he starts to question if he is ready to forgive Addison, leaving his relationship with Meredith hanging in the balance. Cristina recovers from her surgery and proves to be a difficult patient after recieving a visit from her mother. Izzie and Alex's friendship turns into something more, but news from the Cheif distracts Alex and Ellis Grey continues to have the hospital staff running in circles.
Episode number: 05
Original air date: October 23, 2005
Plot:Meredith and Derek are forced to use more than medicine to save a young woman whose beliefs interfere with her treatment, as the time for Derek to make a choice between Meredith and Addison. George shows his true potential during a crisis when a hospital blackout leads him into a career-altering situation while, after his disasterous date with Izzie, Alex shies away from the challenge. On her first day back Cristina faces resolving her feelings for Burke and Richard is reminded of his relationship with Ellis.
Episode number: 06
Original air date: October 30, 2005
Plot: The aftermath of a train wreckage brings an array of critically injured patients to Seattle Grace, and one case forces the doctors to make an impossible choice between two lives, while Meredith nervously awaits to hear Derek's final decision. Alex finds his confidence as a doctor shaken after freezing while George faces the repercussions of his new hero status. Meanwhile, Addison forces Izzie to choose between her allegiance to Meredith and her own ambition when she sees her talent with her specialty.
Episode number: 07
Original air date: November 6, 2005
Plot: In the wake of her scandal, Meredith finds the eyes of the hospital staff are on her and she bonds with a male patient seemingly suffering from a hysterical pregnancy, who also finds himself to be the subject of everyone's gossip and attention. A sheltered patient forces Alex to better express his feelings for Izzie and, after seeing Meredith's treatment after the exposure of her relationship with an attending, Cristina urges Burke to keep their relationship a secret from the Chief.
Episode number: 08
Original air date: November 13, 2005
Plot:Derek and Addison's professional and personal relationship is challenged when their friends from Manhattan come to Seattle Grace seeking a radical, preemptive operation to avoid breast and ovarian cancer. Meanwhile, Meredith's view on love is questioned, George fails to understand why a patient who fell five stories doesn’t seem happy to have survived and Cristina and Burke attempt to have a normal date. The Shepherd's case brings issues in Izzie and Alex's budding relationship to the forefront after their kiss and Richard pushes Bailey for an answer regarding her fellowship offer.
Episode number: 10
Original air date: November 27, 2005
Plot:Meredith is mortified when her one night stand shows up at the hospital suffering an embrassing problem and needing medical attention. Addison's first case as part of the hospital's staff proves to be high profile when she and Izzie are assigned to a woman carrying quintuplets, who is overwhelmed by numerous medical issues as she navigates her high-risk pregnancy. Alex’s shortcomings frustrate Izzie, who starts to make grave mistakes professionally and personally while Burke suprises Cristina by giving her a key to his apartment.
Episode number: 11
Original air date: December 4, 2005
Plot: As the interns all care for the newly born quints, Cristina has little sympathy for her patient, an inmate who jeaprodizes her health to escape solitary confinement. Izzie looks to her friends for support when she feels betrayed by Alex while Addison tries to teach her a painful lesson in order to show her the consequences of growing too attached to patients. George and Olivia clash when they are assigned to the same case.
Episode number: 12
Original air date: December 11, 2005
Plot: The holiday season dawns but not everyone is in a festive mood. Alex faces his last day in the hospital unless he passes his boards practical exam the next day, thus everyone helps him to so that he succeeds leaving Izzie feeling berayed and forcing Meredith of remind her of the true spirit of the Christmas holiday. A young boy needs a heart transplant but doesn't seem to want it, and an argument over his treatment exposes major philosophical differences between Burke and Cristina and despite a reconciliation with his wife, Derek isn't in a festive mood.
Episode number: 13
Original air date: January 15, 2006
Plot: After the Cheif enforces a 80-hour-per-week work limit Meredith and Cristina are forced to take time off and, while Meredith wrestles with Derek and Richard's attempts to get her to allow Ellis to participate in a Alzheimers clinical trial, Cristina joins Bailey on a trip to Idaho for a heart transplant. Izzie gets a new beginning when she finally starts to get over Alex, aided by her undeniable chemistry with heart patient Denny Duquette and Addison and George treat a troubled teenager who they discover to be a hermaphrodite.
Episode number: 14
Original air date: January 22, 2006
Plot:Meredith and Cristina lie to eachother, and themselves, about their relationships with Derek and Burke after Meredith resumes calling him "McDreamy" and Cristina 'kind of' moves in with Burke. George is faced with the difficult task of discharging a defiant patient and Alex finally hears back about the results of his medical boards and turns to Izzie for support. Bailey's pregnancy starts to ineterfere with her surgical career and the Cheif faces pressure from the nurses to ease their heavily increased workload.
Episode number: 15
Original air date: January 29, 2006
Plot: As the nurses of Seattle Grace go on strike the doctors are left to fend for themselves. The interns meet their new resident, Sydney Heron, and while working with her and Alex on a case of flesh-eating bacteria Cristina questions her decision to attempt risky surgery and goes to Burke for an intervention. Treating a pregnant, teenage patient forces Izzie to remember a part of her past she'd put well behind her and Meredith is upset when she learns that Richard has been visiting Ellis, but treating an elderly patient makes her have a revelation about her mother.
Episode number: 16
Original air date: February 5, 2006
Plot:Meredith wakes up with a foreboding feeling that she is going to die and an explosive situation at the hospital places the lives of Meredith and her colleagues on the line as Seattle Grace declares a "Code Black" emergency. Bailey returns to the hospital after going into labour with George and Addison by her side, but not her husband Tucker, and Derek and Izzie are stunned to learn the identity of a patient who suffered serious injuries in a car crash.
Episode number: 18
Original air date: February 19, 2006
Plot:Mark Sloan arrives in Seattle to try and convince Addison to leave Derek and return to him and her life in New York while his presence causes tensions for Derek who is forced to work with his old friend. Burke and Cristina's relationship is tested when one of her secrets is revealed while Meredith is forced to unearth truths about her past and her parents divorce. George debates whether to tell Meredith and how he feel and Izzie stands defiant that she won't sleep with Alex again.
Episode number: 19
Original air date: February 26, 2006
Plot:George and Meredith's friendship becomes strained in the aftermath of their diasterous night together and, while both trying to conceal the truth from their friends, they both struggle to move past what happened between them, while a devestated George attracts the attention of orthopedic resident Callie. Meanwhile, Izzie and Alex's relationship is strained by the return of Denny Duquette and, after Mark's visit to Seattle, Addison and Derek endure some tension of their own.
Episode number: 20
Original air date: March 12, 2006
Plot:George and Meredith continue to feel the aftermath of their night together as George gets closer to Callie as they treat a teenaged patient together and Meredith questions whether or not she can confide in her new friend Derek. Addison treats a patient who gives her more attention than his wife and Derek deals with a couple whose romance was reignited by her diagnosis, forcing them both to make realizations about their marriage and Alex tries to interfere with Izzie and Denny's close relationship. Bailey forces Cristina to care for Tuck when she is called into surgery.
Episode number: 21
Original air date: March 19, 2006
Plot: A series of four deaths on the surgical floor brings out everyone's superstitions as the staff expect three more fatalities. Izzie worries for Denny when he undergoes major surgery and reaches a crossroads in regards to her relationship with Alex when he jealously informs Denny of his chances of death. Cristina taunts Burke when he refuses to kick their new houseguest out of the apartment while Callie grows tired of waiting for George. The arrival of his old sponsor in the hospital forces Richard to reflect on his alcoholism and reassess his relationship with Ellis.
Recurring characters:Sara Ramírez as Callie Torres and Jefferey Dean Morgan as Denny Duquette
Episode number: 23
Original air date: April 30, 2006
Plot:Burke struggles when he treats his musical hero to remove his pacemaker after he claims that it ruined his rhythm. Addison and Alex are conflicted about a pregnant, Catholic patient who requests Addison ties her tubes and hides the procedure from her husband, a request which could compromise Addison’s career. Meredith debates whether or not to accept a date with Finn while Izzie quizzes George on the details of his personal life with Callie. Bailey is on the warpath after Denny lets his relationship with Izzie interfere with medical treatment.
Episode number: 24
Original air date: May 7, 2006
Plot:Meredith and Finn's budding relationship brings about unexpected emotions in Derek who vents his anger and frustration toward Meredith and confronts her while Cristina and Burke's relationship is pushed to the test by a late night faux pas. Izzie is put to task when Denny's physical limitations start to affect his outlook on life while George and Callie face their first bump in the road when he puts his roommates before her. Addison continues to introduce an unwilling Alex to her specialty.
Episode number: 25
Original air date: May 14, 2006
Plot:Izzie is delighted when UNOS finds a heart for Denny, but when problems arise during Burke and Alex’s transplant surgery Izzie makes a choice that could jeopardize her career and Denny’s life in order to secure him the heart. While dealing with the victims of a shooting, George tries to persuade Callie to integrate herself into his family while Addison confronts Derek after he lets his emotions regarding Meredith get the best of him and Cristina feels pushed aside when Burke lets their relationship affect their professional lives.
Episode number: 27
Original air date: May 15, 2006
Plot:Richard interrogates the interns to find out who is responsible for cutting Denny’s LVAD wire and Meredith, George, Alex and Meredith all band together to protect Izzie, whose receives an unexpected offer from a recovering Denny. Tension between Meredith and Derek reaches boiling point after they are forced to make a choice about Doc, leaving Addison and Finn sidelined. Burke and Cristina try to navigate their relationship following his surgery after Burke finds a tremor in his injured hand and Callie reacts adversely when George doesn’t respond to her declaration of love.