From the creators and executive producers of The Job comes Rescue Me, a drama/comedy that centers on the inner workings of Ladder Company 62, a New York City firehouse, and the personal and emotional battles of its members in a post-9/11 world. The show focuses Tommy Gavin, the senior fire-fighter whose life is in turmoil as he copes with the stresses and fears of his job as well the separation from his wife Janet. Tommy moves into a house across the street from her to stay close to their three children and keep an eye on her. The stresses and fears of his job are manifested through conversations with his dead cousin Jimmy Keefe, a former fire-fighter, as well as the haunting memories of people he has watched perish on the job. The remaining heroes of Ladder 62 include Chief Jerry Reilly who, despite being called "The Good Chief," has a serious gambling problem and bets on everything, even Tommy's divorce. Sean Garrity is a young, handsome guy who is easier to look at than hold a conversation with.
Janet has given birth to a baby boy---whom she fears prefers Tommy to her. But Tommy has a bigger problem: He's suspected of starting the beach-house fire. Meanwhile, Jerry's son asks him to be his best man at his commitment ceremony; Richie wants Franco to marry Natalie; Lou and Theresa get distracted in church; and the volunteer firefighter (Jennifer Esposito) who rescued Tommy from the beach house takes an interest in him---and isn't shy about letting him know.
Sheila lies to Tommy when he confronts her about the beach-house fire. But they present a united front to the insurance investigators, as embarrassing as it is for Tommy. Meanwhile, Lou is determined to get a basketball ringer (Larenz Tate) to be 62 Truck's new probie; Uncle Teddy is released from jail; Colleen runs away with her rock-musician boyfriend; and Mike's mother has a deathbed request.
Tommy encounters Colleen's boyfriend and sparks fly; Jerry learns he flunked his physical and is given a desk job; Uncle Teddy, hiding from Ellie, breaks into prison guard Lenny's apartment; Sheila goes out with the man who pulled her from the beach house, while Tommy keeps avoiding Nona (Jennifer Esposito), the volunteer firefighter who rescued him from the blaze; and Mike seeks Tommy's advice on how to deal with his dying mother's request that he kill her.
Emotions flare up when the crew learns about Jerry's death; Tommy's manhood is called into question after some embarrassing romantic encounters; and Lou resorts to blackmail to recruit Bart (Larenz Tate) as the new probie for the house basketball team.
The firehouse gets a new chief (Jerry Adler), who is rumored to possess a very special gift; Tommy suffers embarrassment during a hockey game against the NYPD; Franco works up the nerve to propose to Natalie while Sean tries to talk Maggie out of a divorce; and Sheila makes a surprising proposition as Janet's depression deepens.
Tommy and Janet deal with revelations about the baby; Sean learns a secret that Mike has been trying to hide; the new probie holds the guys to their agreement about doing no 'probie' work; and Lou's cousin Mike visits.
A devastating fire has a profound effect on the crew; Tommy wrestles with his feelings about the baby; Alicia (Susan Sarandon) returns with a proposition for Franco; Troy breaks up with Sheila while Lou makes a tough decision about Theresa; and Sean apologizes to Mike about the fire he set that burned down Mike's mother's house.
Janet plots revenge when she learns what Tommy did with the baby; Franco questions his marriage proposal to Natalie in light of Alicia and Keela's return; and Tommy faces his ghosts.
The Gavin clan stages an intervention after several disturbing family calls; the mysterious woman (Gina Gershon) from the restaurant leaves Tommy wanting more; Janet must take matters into her own hands to get her baby back; and a depressed Mike calls Tommy in a moment of despair
The Gavin family AA group's first meeting doesn't go exactly as planned. Tommy bribes Colleen for information on Janet. Franco learns the truth about Natalie from Richie while Lou contemplates revenge on Cousin Mike.
Tommy goes on another memorable date with Beth for the sake of the crew; Black Shawn proves himself in an unexpected arena; Franco realizes what he's really lost while Latrina shows she knows how to keep Lou happy; Dad gives Tommy some insight into his childhood
Tommy plays hero in someone else's uniform, confusing the crew; Colleen finds a new reason to get upset with Tommy; Natalie asks Franco for a favor; a rift between Mike and Black Shawn nearly leads to blows; and Tommy makes a move on the chief's daughter. This does not please the chief.
In the fourth-season finale, Sheila learns that Jimmy's ghost has been spotted on several occasions, so she investigates. Meanwhile, Colleen blames Tommy for her failed relationship; Franco and Natalie come to an understanding, as do Lou, Cousin Mike and Latrina; and Tommy spends time with his father.