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 decides to meet with Tommy after not speaking with him for months since the sudden death of their son. Uncle Teddy refuses to allow anyone to help him get out prison. Tommy is shocked when he accidentally discovers just who his nephew has been sleeping with.
During a night out, Franco and Tommy meet two women. Tommy is finding himself bribing his daughter Colleen before she tells their mother about his indulgent treatment of her sister Katy. Jerry visits his wife Jeannie in her expensive nursing home and soon goes to Lou for financial help. Meanwhile John Sr. insists on having his 83rd birthday at a restaurant that no one else likes.
Franco begins to fear he's becoming Alicia's boy toy, while Tommy finds a way to end the fling between Damien and his science teacher. The rest of the crew also face their own problems - Lou is becoming real unstable emotionally, the chief has financial problems, and Sean is afraid of Tommy finding out who he's been sleeping with.
The crew decide to save some children from a disabled school bus as they go to call in Harlem. However, the soon meet up with an upset Rev. Al Sharpton. Franco finally realizes why Alicia is so interested in him. Mike and his roommate discuss their sexuality. Sean ends up telling Tommy about his feelings for Maggie. Sheila has a proposal for Tommy. Janet wants to talk to him about their settlement, but with no lawyers involved.
After Sheila bumps into Johnny's ex-wife, Angie, Tommy seeks her out. Jerry and Rose spend a very romantic evening together, while Mrs. Turbody is in jail for statutory rape. This gives Tommy some relief but also new worries, and Franco loses his daughter, Keela.
After a game of street hockey, Sean takes some sleeping pills believing they are painkillers and it has an unwanted consequence. In the meantime, Tommy and Angie decide to go on their fake date that they know will upset Janet. After having a close call, Lou gets a new angle on firefighting from his Uncle Red.
While Tommy and Johnny have another encounter, Janet and Angie re-establish their acquaintance. Meanwhile, Sheila is unhappy when she sees Tommy and Angie together. Maggie wants to get back together with Sean. Mike hooks up with a woman at a bar, making his roommate, Chris, jealous. Franco finds out about Jerry's second job at the pub, and the money in the no-smoking jar goes missing.
Lou turns to new-age techniques in his efforts to change his life. Sean and Maggie come to a surprising decision. Tommy and Angie continue to see each other, which quickly leads to an embarrassing scene with Janet.
The crew faces more than accustomed when rescuing a man from his burning apartment; Sean has a request for Maggie's dad; Franco thinks his new girlfriend is hiding something from him; and Tommy realizes that his crew's future together may be in jeopardy.
Following a meeting with Janet, Tommy has yet another confrontation with Johnny; Teddy's conjugal visits with Ellie prove to be a letdown; and Franco tries to befriend his new girlfriend's mentally challenged brother. Elsewhere, Tommy keeps his vigil at Stack's bedside.
John Sr. ends up disappearing after arguing with Tommy about their living conditions. Tommy is none too thrilled with Lou's latest love interest, while Jerry's new woman might prove to be dangerous for him. Also, Sean and Maggie meet with the priest to discuss their upcoming wedding.
Tommy and Janet are brought together once again by another Gavin family tragedy. Jerry ends up not showing up for work. Mike decides it is time to look for some advice about his sexuality. Meanwhile, Maggie has a surprise for Sean.