Second year residents Abby Lockhart, Neela Rasgotra and Ray Barnett have now become the teachers. And Dr. Archie Morris (Scott Grimes) realizes he makes a better manager than a doctor. Dr. Pratt resolves issues with his family through his estranged father (Danny Glover), while a new attending doctor (John Leguizamo) poses as a patient to test the knowledge of the ER staff, causing friction with Dr. Kovac that leaves Abby caught in the middle.
In the 12th season premiere, Sam and Kovac report to the police that her diabetic son, Alex (recurring guest star DOMINIC JANES), is missing and is possibly trying to find his father. The boy mistakenly thinks his dad is in Colorado, but the man is actually incarcerated.
Ray attends to Claire (ERIN COTTRELL), a surrogate mother who goes into premature labor after being involved in a car accident. Claire refuses a cesarean section even though the unborn baby is in fetal distress, forcing the doctors to make an emotional decision.
The emergency room is jolted when a new nurse manager, Eve Spellman (recurring guest star Emmy Award winner KRISTEN JOHNSTON - "3rd Rock from the Sun"), enforces her strict and efficient new procedures. Kovac and Sam are uncomfortable working together on the same shift. Meanwhile, Abby treats a breast cancer patient who is having a hard time accepting her condition.
A patient who has been in a coma for nine years suddenly awakens in the emergency room, and Kovac struggles with whether he should reveal to her the truth about her past. Abby comforts Dr. Otis Dubenko (recurring guest star LELAND ORSER - "The Bone Collector," "Daredevil") after he finds out some troubling news.
Pratt gets a surprise when the new attending doctor, Victor Clemente (recurring guest star JOHN LEGUIZAMO - "Spawn," "Moulin Rouge!"), poses as a patient to test the knowledge of doctors in the emergency room. Meanwhile, Kovac bonds with his former coma patient and contemplates bending the rules for her.
Clemente (recurring guest star JOHN LEGUIZAMO), Abby and Neela secretly care for a very important patient while Dubenko (recurring guest star LELAND ORSER) tortures the emergency room staff via a robotic television camera from his home. Sam is coerced into accepting a management role and is given a dreadful task.
Neela prepares for Gallant's (SHARIF ATKINS, not appearing in this episode) homecoming from the war, but her plans change when she receives a call from Iraq. Meanwhile, when Kovac and Clemente (recurring guest star JOHN LEGUIZAMO) disagree on how to save a patient's life, Abby gets caught in the middle. A police officer and a little girl are victims of a shootout, and Neela is conflicted about whether or not she should save the gunman's life. Recurring guest star JOHN STAMOS appears as paramedic Gates.
Neela rides along with ambulance driver Gates (recurring guest star JOHN STAMOS). They respond to a huge emergency after two commuter planes crash in midair and land on a densely populated area of Chicago. Many passengers and pedestrians are injured, and other victims are trapped inside a burning building.
After returning from Iraq, Gallant (recurring guest star SHARIF ATKINS - "Eve," "The Big Time") surprises Neela by telling her he wants to take their relationship to the next level. Kovac and Clemente (recurring guest star JOHN LEGUIZAMO) vie for the same job--increasing the obvious tension between them.
After a little girl is mistakenly shot, Pratt and Weaver desperately try to revive her. Meanwhile, Haleh (recurring guest star YVETTE FREEMAN) holds her annual choir tryouts, and everyone is surprised by who is chosen to sing the solo. Eve's (recurring guest star KRISTEN JOHNSTON) treatment of a patient causes management to get involved.
Abby struggles with the decision of whether or not she is ready to become a mother. Meanwhile, Neela and Kovac help a religious teenager weigh all of her pregnancy options. Ray gets a once-in-a-lifetime opportunity with his band, and everyone is shocked at the outcome. Clemente's (recurring guest star JOHN LEGUIZAMO) past catches up with him when the police search for him in the emergency room.
Clemente (recurring guest star JOHN LEGUIZAMO) is missing, and Dr. Dubenko (recurring guest star LELAND ORSER) volunteers to take the dayshift but ends up feeling overwhelmed. Ray is put in a very awkward situation when his young former girlfriend comes into the emergency room with serious abuse-related injuries.
When an abandoned patient with Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease) arrives at the emergency room, many of the doctors are shocked to recognize former medical school professor Dr. Nate Lennox (JAMES WOODS - "Salvador," "Ghost of Mississippi," "Be Cool"). Abby and Kovac try to understand Nate's wishes after the professor is struck with pneumonia in addition to the nerve degenerating disease.
Clemente (recurring guest star JOHN LEGUIZAMO) and his girlfriend, Jodie (CALLIE THORNE), have a great time together until they are suddenly interrupted by Jodie's husband, Bobby (SHEA WHIGHAM). When Jodie threatens divorce, Bobby takes matters into his own hands.
Dr. John Carter (former series star NOAH WYLE) is joined by Dr. Dakarai (recurring guest star EAMONN WALKER - "Oz") in the Sudanese desert as they treat hundreds of disease-infested and famine-stricken people. Carter and Dakarai spring into action to save a woman who was raped by a militant group.
Weaver contemplates hip replacement surgery after she finds it hard to do her labor-intensive job. Meanwhile, Kovac tries to ease Abby's fears about raising a child together. Neela decides to attend a support group for military spouses, but when she offers her opinions on the war, the meeting turns into a debate.
When a 21-year-old woman is brought into the emergency room with stab wounds to the neck, Abby and Kovac desperately try to keep her alive while they wait for a surgeon to operate. As the victim's condition begins to deteriorate, Clemente (recurring guest star JOHN LEGUIZAMO) steps in and attempts a risky procedure in order to save her life.
When police bring in two teenagers involved in a car accident, Abby and Morris struggle to figure out what is wrong with the unconscious girl, while police try to interrogate the other teen. Meanwhile, Neela gets a visit from her in-laws, Colonel James Gallant (recurring guest star ERNIE HUDSON - "Ghostbusters") and Mrs. Gloria Gallant (recurring guest star SHERYL LEE RALPH - "Barbershop"), and receives some troubling news.
Abby becomes suspicious when a woman, Mrs. Pooler (DIANE LADD), and her 12-year-old granddaughter arrive at the hospital. When Sam's imprisoned ex-husband is brought into the emergency room, the doctors assume he is faking his condition, but further tests prove otherwise.
Pratt settles into his new job in Darfur but is troubled by the astounding number of people needing care. When a sheik and his pregnant wife come into the camp, Carter (former series star NOAH WYLE) and Dakarai (recurring guest star EAMONN WALKER) operate on the man's gunshot wound--but they are quickly interrupted by government officials trying to arrest the patient.
Having just returned from Darfur, Pratt struggles to get the real story from two abused boys who came into the emergency room with their injured father. Neela becomes nervous when she is urgently called up to Dr. Dubenko's (recurring guest star LELAND ORSER) office, but she is quickly relieved to hear what he has to say.
Chaos strikes when two injured convicts come into the emergency room and try to escape the authorities. With the help of an accomplice posing as an emergency medical technician, the fugitives involve one of the nurses in the melee. As the gunmen get more and more desperate to make it out of the hospital, they resort to extreme measures, putting Kovac in harm's way.