In the fifth-season opener, Meredith and Derek discover the morning-after side of their renewed relationship; a military doctor (Kevin McKidd) who arrives at the hospital with a trauma patient catches Cristina's eye; and the chief learns that Seattle Grace's national rankings have slipped. Sarabeth: Bernadette Peters. Betty: Mariette Hartley. Anna: Kathy Baker.
The chief attempts to implement new teaching policies, and George tries to retake his residency exam as flooding from a plumbing leak causes major problems at Seattle Grace. Meanwhile, Derek wants Meredith's roommates to move out of her house, to their surprise. Barry: Daniel J. Travanti.
Meredith gets upset when Derek finds her mother's diary; Callie worries about her first "official" date with Erica; and Cristina discovers a part of the hospital that neither she nor her fellow residents had seen before.
Bailey heads up a "domino procedure," in which each surgery hinges on the one preceding it. Meanwhile, Derek gets sole credit for the brain-tumor study he did with Meredith; Lexie tries to get George to notice her romantically; and Sloan counsels a desperate Callie in the ways of love.
The chief gives Bailey new power and responsibility. He also gives her a very difficult surgical assignment: remove a girl's inoperable tumor. Meanwhile, new trauma chief Owen (Kevin McKidd) challenges the attendings' methods and the residents' skills.
The Chief tells the residents that one of them will get a solo surgery, and a competitive frenzy ensues; Derek asks Bailey for advice when he feels that Cristina is coming between him and Meredith; Erica discovers a shocking connection between one of her residents and a longtime patient.
Meredith's old friend Sadie (Melissa George) becomes an intern at Seattle Grace, but Meredith's other friends aren't exactly welcoming; new surgeon Virginia Dixon (Mary McDonnell) brings rules and order to the OR; and Lexie leads the interns in secretive, unorthodox surgical-training sessions.
A routine surgery goes horribly awry for Lexie and Sadie, so Meredith, Cristina and Bailey rush to assist them. Meanwhile, Owen and Derek treat a man who was injured while sleepwalking, and Mark comforts the man's daughter.
Cristina is awarded the first solo surgery among the residents, but she has to relinquish it and choose her replacement; Mark performs a cutting-edge procedure to restore a patient's speech, impressing Lexie in the process; and Callie can't figure out if Sadie (Melissa George) is flirting with her or just being friendly.
While Bailey teams with new pediatric surgeon Arizona Robbins (Jessica Capshaw ) to save a young patient near and dear to her heart, the arrival of a death-row inmate at the hospital angers Derek and further erodes Meredith and Cristina's friendship. Meanwhile, Callie and Sloan join forces to fight their respective attractions to Sadie and Lexie; and Izzie tells Alex that she has been seeing Denny (Jeffrey Dean Morgan). William: Eric Stoltz. Melinda: Samantha Mathis.
Derek's mother, Carolyn (Tyne Daly), meets Meredith for the first time during a surprise visit to Seattle, and Mark tries to conceal his relationship with Lexie. Meanwhile, death-row inmate William (Eric Stoltz) wants to donate his organs to Bailey and Arizona's patient; and Owen and Cristina attempt to go on a first date. Arizona: Jessica Capshaw. Denny: Jeffrey Dean Morgan. Melinda: Samantha Mathis.
As her young patient's condition worsens, Bailey seeks desperately for an organ donor. One possibility: death-row inmate William (Eric Stoltz). Meanwhile, an injury leaves Mark in a compromising position in the OR, and Cristina tries to avoid Owen, and she looks foolish doing so. Arizona: Jessica Capshaw. Melinda: Samantha Mathis. Denny: Jeffrey Dean Morgan.
Engagement ring in hand, Derek searches for the right way to propose to Meredith. Meanwhile, Lexie demands that Mark go public with their relationship; and Bailey considers a new direction for her medical career, encouraged by Dr. Dixon (Mary McDonnell) as well as her work on recent cases.
In a "Private Practice" crossover episode, Addison, Naomi and Sam rush Addison's ailing brother, Archer (Grant Show), to Seattle Grace in an effort to save his life. Meanwhile, Owen runs into a significant someone from his past; and Izzie employs her fellow doctors in a medical game designed to help teach the interns.
Derek's confidence is shaken when he and Addison (Kate Walsh) disagree on treatment for a pregnant woman who's dying; Cristina questions the abilities of a renowned surgeon (Faye Dunaway) after she botches a standard procedure; and Bailey, who has decided to pursue a fellowship in pediatrics, is appalled by the chief's less-than-stellar recommendation letter.
Derek decides to quit after learning of a high mortality rate among his patients; Bailey and the chief continue to spar over her pediatrics fellowship until Adele (Loretta Devine) steps in; Izzie's interns find something disturbing about a Patient X.
While Mark attempts a face-transplant surgery, Meredith tries to get Derek to return to work after his fellow surgeons fail in their attempts. Meanwhile, Cristina finally gets a solo surgery, but she's more focused on the needs of her friends; and Izzie tries her best to keep her condition a secret.
While Derek prepares to perform his first surgery since his breakdown, Izzie must undergo one. Meanwhile, Owen has another PTSD episode, which injures Cristina, traumatizes both of them and throws their relationship into question. Dr. Swender: Kimberly Elise.
Izzie won't let her taxing cancer treatments stop her from helping to plan Meredith and Derek's wedding. Meanwhile, Callie's father (Hector Elizondo) isn't happy when she introduces Arizona as her girlfriend to him; George shines---and Alex doesn't---in a trauma surgery; and Owen seeks out help for his post-traumatic stress disorder.
Izzie's mother (Sharon Lawrence), who's something of a handful, shows up at Seattle Grace, while Meredith and Lexie receive a visit from their father (Jeff Perry), who's sober and sorry for past sins. Meanwhile, Meredith and the Chief fight about a case, and preparations continue for Meredith and Derek's wedding. Julie: Kellie Martin.
As Meredith and Derek's wedding nears, college students are rushed to the ER following a car crash on their way to graduation ceremonies. Meanwhile, Izzie experiences familiar symptoms.
Season 5 finale: Izzie decides whether to undergo cancer surgery; Mark prepares to move forward with Lexie; Bailey learns whether she'll get her pediatric fellowship; George makes an announcement; and Owen makes a reassessment. Meanwhile, the doctors work as a team following an auto accident.