The season featured 13 actors credited in a starring capacity. All of the fourth season cast members returned and all were credited for the full season with the exception of Brooke Smith who departed the series and ceased being credited after her character Erica resigned from Seattle Grace in the episode "Rise Up".
Kevin McKidd joined the principle cast mid-way through the season. McKidd first played Owen in the season premiere and acted in 11 episodes in a recurring capacity until the episode Beat Your Heart Out in which the character was elevated to a permanent role.
Episode number: 01
Original air date: September 25, 2008
Plot:Meredith questions if she and Derek can have a happily ever after in the wake of their reunion while Cristina tries to force Meredith to see that she and Derek, once again, will not work together. The doctors are rocked by the news that the hospital's ranking has fallen significantly while Mark taunts Lexie about her feelings for George. An incoming trauma brings Major Owen Hunt to the hospital and his radical idea to save Callie and Derek's patient causes conflict while Alex and Izzie's newfound friendship develops.
Episode number: 02
Original air date: September 25, 2008
Plot: While the deadly snowstorm continues to ravage the hospital, Owen rescues Cristina after a falling icicle injures her while a patient causes Meredith to reconsider whether moving in with Derek is a good idea. Derek and Rose's relationship grows hostile while Callie leads a radical freezing procedure to save a patient and boost the hospital's fading status. Alex reacts badly when he realizes how Izzie now sees him while the Chief is forced to reassess how his hospital runs in the wake of Seattle Grace being ranked #12.
Episode number: 03
Original air date: October 9, 2008
Plot: A plumbing leak becomes a deluge and wreaks havoc at Seattle Grace, and interferes with the Chief's attempts to implement his new teaching regime and George's efforts to retake his intern exam. After moving in with Meredith, Derek pushes her to kick her roomates out out while Meredith causes concern when she quits therapy. Alex continous to act callously to Izzie when she suggests they get an apartment together and Lexie believes she can explain a patient's seven-year headache.
Episode number: 04
Original air date: October 16, 2008
Plot:Cristina discovers a new part of the hospital that neither she nor her fellow residents had seen before as Meredith gets upset when Derek finds her mother's diary resurfacing her complexion about measuring up to her mother's surgical skill. George and Lexie await news about the results his intern exam and Callie grows nervous about her first official date with Erica. Izzie is forced to fight back when Alex steals her surgery.
Episode number: 05
Original air date: October 23, 2008
Plot:Bailey heads up a "domino procedure," in which each surgery hinges on the one preceding it, and the residents are all assigned to help her make sure it goes smoothly while they all debate which of their interns to give to George now that he's a resident. When their clinical trial is published, Meredith grows bitter when Derek gets all the credit and, after an uneasy night with Erica, Callie turns to Mark to teach her his skills. Izzie continues to struggle with Alex.
Episode number: 06
Original air date: October 30, 2008
Plot:Owen Hunt returns to Seattle Grace as the new trauma attending and, as he tests the skills of the residents and attendings, his techniques cause issues from the staff while Cristina is thrown by his presence in the hospital. Meanwhile, Richard gives Bailey very difficult surgical assignment: removing an inoperable tumour and she, Erica and Meredith are put to task to save the patient. Lexie struggles to hide her anger at George and Izzie and Alex's relationship gets off to an unsteady start.
Episode number: 07
Original air date: November 6, 2008
Plot:Izzie begins to feel haunted by her past when she man she stole the heart from for Denny years ago arrives in the hospital needing treatment while Erica is stunned to learn of the connection between her patient and her resident and reacts adversley. Meanwhile, the Chief announces that one of the residents will soon be performing the first solo surgery prompting a competitive frenzy. Lexie strives to find alternative ways to learn and Derek enlists Mark to help stop Cristina coming between him and Meredith.
Episode number: 08
Original air date: November 13, 2008
Plot: The arrival of Meredith's old friend Sadie gives Derek an insight in Meredith's past while Izzie tries make sense of Denny's recent appearances in her life as she searches for a way to get rid of him. In the wake of Hahn's departure, Bailey is assigned with wooing new surgeron Virgina Dixon, who brings rules and order to the O.R and Callie tries to cope with her departure. Lexie leads the interns in secretive, unorthodox surgical-training sessions.
Episode number: 09
Original air date: November 20, 2008
Plot: The interns attempts to teach themselves leads to Sadie suggesting the others remove her appendix but, when the routine surgery goes horribly wrong Bailey, Meredith and Cristina must come to Lexie's aid to save Sadie's life. Owen acts on his feelings for Cristina while Izzie's visions of Denny become more persistent putting a strain on her relationship with Alex. Owen and Derek treat a man seriously injured while sleepwalking and Mark comforts the sleepwalker's distraught daughter.
Episode number: 10
Original air date: December 4, 2008
Plot:Cristina is awarded the first solo surgery but, as a punishment from the Chief has to relinquish it and choose which of her fellow residents should perform the surgery while her feud with Meredith escalates. Izzie struggles to balance her relationship with Alex with her visions of Denny. Mark performs a cutting-edge procedure to restore a patient's speech, impressing Lexie in the process and Callie tries to work out if Sadie is being friendly or flirty.
Episode number: 11
Original air date: January 8, 2009
Plot: The arrival of a death row inmate solicits anger in Derek and further erodes Meredith and Cristina's already tense friendship while, after the unexpected death of the hospital's peadiatric attending, Bailey clashes with his replacement Arizona Robbins over the course of treatment of a patient near and dear to her heart. Izzie tells Alex about her visions of Denny and Mark and Callie work as a team to fight their respective attractions to Sadie and Lexie.
Episode number: 12
Original air date: January 15, 2009
Plot:Derek's mother arrives in Seattle and meets Meredith for the first time while treating the death row inmate continues to force Derek to face his demons while Meredith struggles with how to react when her patient offers to donate his organs to Bailey and Arizona's ailing peads patient. Mark's attempts to conceal his relationship with Lexie go awry. Owen asks Cristina out on a date and Izzie is forced to reasses her relationship with Alex and her visions of Denny.
Episode number: 13
Original air date: January 22, 2009
Plot:Bailey grows desperate as a patient's condition becomes more and more dire. Everyone in the hospital is stepping up to try to find the boy a new organ donor, including Meredith, who considers a death row patient's wish to die before execution. Cristina avoids Owen after their disasterous date and Izzie finally learns why Denny has been appearing to her. His secret relationship with Lexie's causes unexpected problems for Mark.
Episode number: 14
Original air date: February 5, 2009
Plot: Now that he has the engagement ring, Derek searches for the perfect way to propose to Meredith while Owen and Cristina's relationship goes from strenght to strenght until a face from his past arrives in the hospital. A case with Virginia Dixon makes Bailey consider a new direction for her medical career. Izzie finds a way to teach the interns as she tries to diagnose herself and Lexie pushes for Mark go public with their relationship.
Episode number: 16
Original air date: February 19, 2009
Plot:Derek's confidence is shaken like never before as he faces off with Addison over what course is best for their dying pregnant patient whule trying to amend a mistake he made in a patient's surgery. Bailey is far from impressed by the Chief's far from stellar recommendation letter Izzie makes a devestating realization when she learns of an intern's mistake with a patient. Cristina calls the abilities of a renowned surgeon into question after she botches a standard procedure.
Recurring characters:Kate Walsh as Addison Montgomery and Jessica Capshaw as Arizona Robbins
Episode number: 17
Original air date: March 12, 2009
Plot: After making a mistake in the O.R which cost a patient their life, Derek spirals into a depression and, after learning his death rate statistic, decides to quit surgery in spite of Meredith's insitance that she won't give up on him. Izzie presents the interns with 'Patient X' in a bid to teach them while trying to come to terms with her own mortality and Bailey and Richard continue fight over her peads fellowship. Alex must go head to head with Owen and Arizona in order to save a life.
Episode number: 18
Original air date: March 19, 2009
Plot:Derek remains absent from the hospital and Bailey rallies the staff together in order to get him back to work while Richard searches for a way to help Derek finds his way when he begins to feel hospital is falling apart. Cristina is finally awarded her first solo surgery but is distracted by her concerns about Izzie's treatment, who begins to question if she wants surgery. Mark leads a radical new procedure and Meredith and George cope with intern drama.
Episode number: 19
Original air date: March 26, 2009
Plot: All eyes are on Derek when he returns to work to perform surgery on Izzie and he finds himself questioning if he's ready to enter the O.R again while the residents do their best to comfort Izzie on her first day as a patient in the hospital. Alex struggles to be there for Izzie in her time of need and George is crushed to learn that he was the last to learn of her ailment. Owen's nightmare becomes near catastrophic for Cristina and leaves them both traumatized.
Episode number: 20
Original air date: April 23, 2009
Plot: Amidst a series of intense treatments, Izzie throws herself into Derek and Meredith's wedding plans and she tries to remain optimistic while her treatment begins to take it's tolll on her. George catches the eye of Owen when he excels during a trauma case while Alex freezes. Bailey learns of the heart-wrenching practices in peads while Callie's father arrives in Seattle and is far from pleased to learn of the drastic change in her life. Lexie tries to mend the rift between Derek and Mark.
Episode number: 21
Original air date: April 30, 2009
Plot: As preparations for the wedding continue, Thatcher returns to Seattle Grace, now sober, in a bid to make amends with Meredith and Lexie and Meredith's issues with the Chief and his past with her family are brought to the surface when she and Richard clash over a controversial medical case. Izzie faces the arrival of her mother who pays a surprise visit after learning of her daughter's ailment. Callie tries to adjust to life without her trust fund and Lexie tries to get Mark to meet her father.
Episode number: 22
Original air date: May 7, 2009
Plot:Meredith and Derek's wedding day arrives, Izzie fears the worst when she begins to experience familiar symptoms and the reoccurance of her visions leads Derek to make a discovery about Izzie's illness and an unexpected suggestion to Meredith. Owen, Callie, George and Lexie deal with a group of college students admitted to the E.R after a crash on their way to their graduation. Callie's monetary issues interfere with her relationship with Arizona while Cristina gets an insight into Owen's trauma.
Episode number: 23
Original air date: May 14, 2009
Plot:Izzie spends time with a fellow cancer patient and contemplates whether or not to undergo a risky surgery while Alex, Meredith and Cristina each try to advise her to take the course of treatment they think is best. Meanwhile, treating a young solider prompts Owen and George to reasess their futures at the hospital. Arizona is forced to fight back when the Chief tries to lure Bailey back to general surgery while Mark tries to move forward in his relationship with a reluctant Lexie.
Episode number: 24
Original air date: May 14, 2009
Plot:George delivers news that send shockwaves around the hospital while Seattle Grace must come together to save the life of a trauma victim, but Meredith makes a revelation that no one could see coming. The doctors all anxiously wait for Izzie's recovery from her surgery. George's decision brings about a difference of opinion between Callie and Arizona while Bailey faces a difficult choice when her husband makes her choose between their marriage or her peads fellowship. Cristina makes a choice about her future with Owen.