A group of detectives and officers work at the 15th Precinct, a seedy police station in Manhattan, New York City. Detective John Kelly, a 15-year veteran of the force, deals with his partner Andy Sipowitz, an alcoholic 20-year veteran detective. Laura Michaels, an aspiring lawyer and Detective Kelly's wife, is having problems with their marriage and she hires Josh Goldstein, a lawyer who lives in apartment 4B of their building to work on a divorce, who gets mugged in the laundry room of the building. Meanwhile, Sipowicz is relentlessly pursuing mobster Alfonse Giardella, who threatens Sipowicz to leave him alone. Later, Sipowicz is shot by Giardella during a tryst with a prostitute. Enraged, Kelly orders the precinct officers to hound Giardella and his ruthless employer; mafia kingpin Angelo Marino. The new patrol officer, Janice Licalsi, is attracted to Detective Kelly. But is she is revealed to be an informant for Marino who orders her to murder Kelly.

Inspector Lastarza of the Organized Crime Unit tells Lt. Fancy and Kelly that they stop applying pressure to the local mob for their pursuit of Angelo Marino is hurting the FBI investigation to nail Marino. Meanwhile, Sipowicz regains consciousness in the hospital after the shooting, but he has no memory about the attempt on his life because he was drunk at the time. Laura and John Kelly become officially separated and she decides to join a private law firm. Josh "4B" Goldstein becomes more paranoid about his mugging and brings a gun into the laundry room every night in hopes to catch his attacker. Kelly tries to reason with a deranged man who has taken a judge hostage who let his son's killer free. Elsewhere, Angelo Marino puts more pressure on Janice to murder Kelly, but she kills him and his chauffeur/bodyguard instead and slips away.

Russell worries about her mother's pending grand jury trial for the intentional murder of her father. Meanwhile, Sipowicz and Simone search for the killer of a mobster's son, that reveals a family affair. The pompous lawyer of a suspect in another murder case impedes Medavoy and Russell's investigation and the erratic behavior of son of the victim doesn't help much either. Also, Martinez and Lesniak investigate another murder case that may be connected to Sipowicz and Simone's murder suspect who now may be on a killing rampage.

Simone and Sipowicz investigate a murder, but the procedures they must follow make them unpopular at the precinct when a fellow cop might have been involved. Meanwhile, Medavoy and Kirkendall investigate the murder of a young girl where the only clue is a videotape that starred her crushing worms. Russell goes missing and eventually turns up in Simone's apartment where she recalls to him that her father molested her as a child.

In the four months since Joey Salvo's assassination, Simone is working odd jobs since he has been suspended by Internal Affairs pending their investigation, while he approaches Sipowicz asking about his and others incitements by the FBI who think that Salvo's death was an inside job within IAB, and Lt. Shannon from IAB tells Lt. Fancy that he may know the person who killed Salvo. Meanwhile, Gina discovers herself to be pregnant, but is hesitant on telling Martinez.

Sipowicz is visited by an old school friend who asks him to help talk to his daughter about the company she is keeping, which takes a turn when the woman's roommate turns up murdered and Sipowicz thinks that another one of his old high school friends was involved. Meanwhile, Medavoy and Martinez look into a case where a man is getting a lot of teeth that contain gold fillings and they uncover a small grave robbing operation. Simone overhears Naomi talking with a different accent, and she tells him that she is actually from Australia and about her desire to become a policewoman.

Simone and Sipowicz look into the shooting of two women (one of whom was killed) who were raped by a group of men in an apartment owned by a former crack dealer, named Jamal, who was crippled in a previous shooting incident. Sipowicz confides in Simone about his medical condition when Simone sees Sipowicz's doctor pull him aside and talk to him confidentially. Meanwhile, Kirkendall, Russell and Medavoy investigate a shooting at a clinic. When they get a woman suspect into custody, a security guard from the clinic who was her secret admirer comes to the precinct demanding she get a second chance.

The detectives search for the truth when a white off-duty police officer with a history of racism fires upon an African-American undercover cop. Dolores is arrested for shoplifting.

The squad attends a homicide with seven naked bodies. Jill's ex is arrested.

A man loses his penis. Fancy makes Captain and the incoming Lieutenant is a ball-breaker. Andy is having second thoughts about Cynthia. A mob hit-man sings like a canary and implicates a celebrated Customs officer.

When Clark's badge is stolen, the squad scrambles to find the thief before Clark must report the loss, which could ruin his career. McDowell and Gibson investigate a murder involving a young pregnant girl.

The detectives investigate the bombing of an abortion clinic that killed a guard. The squad gets a new lead on an old murder case. Ortiz's husband, Don, is murdered by his mistress' husband.

McDowell and Ortiz investigate the death of a woman found in her apartment, where an ex-con neighbor is suspect. The investigation into Scott's murder points towards his friend. Andy thinks about the future. Rita meets John's father.

Connie struggles to settle with the baby. A woman is found dead in a vacant lot. Another is found dead in the laundry room of her building. The Lieutenant dresses up for a lunch.

When NYPD Auxiliary Police Officer Heather Peterson is murdered, the detectives find her diary that details the sexual habits of the police officers at the 15th precinct. These findings cause the detectives to suspect the officers of the 15th precinct had something to do with her death, and the investigation of the cops cause tension between the officers and the detectives.

Sipowicz and Clark investigate when Julian Pisano is wounded in a shooting incident; McDowell and Ortiz assist a woman who doggedly pursues justice when she's conned out of $100; Clark grows concerned when his father stops returning his phone calls.

Sipowicz, Russell, and Clark attempt to connect the murder of a young woman to two other killings; Medavoy and Jones investigate the shooting death of a mother whose children feared her.

A man armed with a bomb walks into the station house and handcuffs himself to McDowell; unless the detectives release a Russian mobster from jail in one hour, the bomb will detonate.

Teacher David Lewis comes into the squad-room to talk about Cindy Clifton and a support group that he ran that she was a part of. Sipowicz and Clark let him go but send off some of his left behind chewing gum to DNA for testing. Jones goes to court as its the day when Michael is to testify against his father. Ortiz and Ronson go to the scene where tourist Ned Applebaum has been mugged and lost his wife's $35,000 necklace. Ortiz and Ronson eventually find out that Ned met a lady friend on the Internet and he was going to meet her in Little Italy when he was mugged. He was going to loan her the necklace so that she could use it as collateral for a loan for her sick child. The detectives get the PO Box number where Applebaum had sent previous gifts to his lady friend. Ortiz and Ronson go to the apartment of the owner of the PO Box. He is a day trader/con artist who they discover took advantage of Ned Applebaum. They get the necklace back and Ned is forgiven by his wife. Later, Gibson tells Sipowicz and Clark that David Lewis was found DOA in his apartment. They go to the scene and try to determine whether the death was a suicide or not. Sipowicz tries to decide how to proceed with the investigation of Lewis's death; both he and Clark believe that Brockhurst might be involved. Clark gets a call about Dr. Jennifer Devlin and goes to the hospital. The doctor tells her she needs to remain restrained for now, but he is allowed to see her as long as he doesn't loosen her restraints. Sipowicz finds Brockhurst and tells him of his theory that he killed David Lewis. Brockhurst doesn't admit to anything, but tells Sipowicz he is going to be able to sleep tonight now that the case is closed.

The detectives protect a scared witness testifying in a felony murder trial; Michael's father wants to regain custody; Bale finds out about Medavoy's job at the bar.

The detectives investigate the smothering death of an elderly man married to a voluptuous woman in her 20s; and a state judge pressures Medavoy and Jones to find out who poisoned her mother.