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Detectives from NYPD's 15th Precinct investigate homicides within their precinct.

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Simone and Sipowicz investigate a crime where a man discovers a woman's body stuffed inside a large box. While on the case, they meet the victim's brother, a strange man who is more concerned with drinking a particular brand of soft drink. Meanwhile, Russell investigates the death of a child whose parents do not seem fit to raise a child. Also, Kirkendall and Medavoy look into the death of a young boy whose very religious parents suggest that the person who killed their son can be forgiven.

Simone returns to work at the 15th Precinct and immediately helps Sipowicz with his case of the shooting death that occurred during a robbery at a local bar. Meanwhile, Martinez and Medavoy stake out a hotel where a serial rapist has been committing his crimes. Gina finally accepts James' proposal and wants a quick wedding.

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.

The detectives investigate a grisly murder in which an elderly woman's hands and feet were cut off. Simone's health continues to deteriorate.

The detectives of the 15th Precinct investigate a double homicide involving one of their own, an alcoholic cop who seems to have done the right thing, but can't remember key details about the incident.

Simone and Sipowicz investigate a break-in of a high-rise apartment where the wife and baby are killed and the husband injured. Vince Gotelli, now an insurance adjuster, tells Simone and Sipowicz that the man may have faked a break-in to kill his family to collect an insurance policy. Meanwhile, Fancy gets some clues about a 15-year-old unsolved murder case from a visiting old friend who is dying. Also, Russell, Martinez, and Medavoy investigate the murder of a record company executive who wasn't very popular among his co-workers.

Simone and Sipowicz investigate the murder of a nurse where the suspects include a struggling actor, a crazy man, and eventually a uniformed officer from the precinct named Tommy Richardson. Meanwhile, Medavoy and Kirkendall look into the death of a bicycle messenger who was killed for just trying to help a man whose backpack was stolen, so they determine that the backpack contained drugs. When they get a suspect into custody, Kirkendall figures out a clever way to get an ID on the suspect who won't cooperate. Also, Sipowicz's doctor tries to talk to him about how to deal with his medical problem, but Sipowicz won't listen.

Sipowicz returns to work after his successful prostate surgery, but apparently too soon, for he has an accident while interrogating a suspect. He is given desk duty to help Simone and Russell investigate the murder of a woman's boyfriend by her ex-husband, the ex-husband later revealed to be searching for his daughter who's gone missing while in the ex-wife's care. Meanwhile, Simone is called upon by Detective Nick Savino to help investigate a missing persons report that is being filed by the nephew of one of Simone's apartment tenants. Based upon past exchanges between the missing woman and Henry Coffield, another building tenant, Coffield becomes a suspect. Former administrative aide Naomi Reynolds shows up at the station, now wearing a private security uniform and speaking in her natural Australian accent, to visit Simone, hoping to tell him that her situation with the INS was resolved and she is now furthering her pursuit to one day become a NYC police officer.

Sipowicz helps his ex-wife deal with a drunk-driving violation. Simone's body rapidly succumbs to infection in the wake of his heart transplant.

Simone and Sipowicz work with Cohen to investigate the death of one of Cohen's witnesses and her son. Evidence points to the opposing attorney having some involvement with the arrangement of the homicide. Meanwhile, Russell and Kirkendall try to help a man locate his missing daughter. Medavoy and Martinez look into a corporation dealing with fake sports memorabilia, where Medavoy is taken in with the blond employees who reminds him of the departed Donna. Also, when Sipowicz thinks about his low sexual functions, his doctor prescribes the wonder drug Viagra. In the mist of all the cases, Simone and Russell decide to get married on their lunch break, but their cases get in the way of it all.

The detectives get a break in a case involving a police officer suspected of committing murder.

Simone and Kirkendall work on a murder case where a son is bitter about his father's death and offers $5,000 to anyone who can produce the killer, and the result is a greedy horde of people with many false leads. Meanwhile, Sipowicz and Russell investigate the rape of a nine-year-old girl, whose mother thinks the culprit may be a retarded boy from their apartment building.

Simone and Sipowicz investigate the disappearance of a young boy, who turns up dead and the father points that a mute homeless man, named Israel, may have been the one. But Supowicz suspects that the father may be the real culprit. Meanwhile, the rest of the squad investigate the murder of a Hasidic Jewish girl and have to juggle the need for their investigation against the needs for a quick burial.

After Israel hangs himself, Sipowicz investigates a clue which is a bible verse that Israel pointed out to him, which leads Sipowicz and Simone to set up a complex sting operation to find out if the father of the murdered boy really was the one that set the whole Israel frame-up. Meanwhile, Medavoy and Martinez look into a doctor who is helping out the homeless by getting them a job with insurance benefits that he helps collect.

The detectives question a group of unsavory suspects after a well-dressed man is found dead in a park. The squad tries to stay optimistic as Simone is told that he will require a heart transplant.

As Sipowicz prepares for prostate surgery with Sylvia by his side, James Martinez returns after recovering from his back problem where he reports that Gina had her baby three weeks earlier. But Medavoy is even happier after returning from upstate New York with a videotape of Abby giving birth to her baby and is very eager to show the tape to anyone who will watch. Meanwhile, the rest of the squad gets involved in a case of five reuniting Army buddies when one of them is found dead. The four others try to keep their fabricated story straight as Simone and the others try to figure out their involvement.

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.

A murdered couple is found where the dead man is a car salesman and the woman is a prostitute. Simone and Sipowicz look into the salesman's death, while Medavoy and the other detectives look into the prostitute's death, where the M.O. of the suspect is to buy used condoms from a prostitute and then mix the spent semen with his own to cover his crime. As Sipowicz recovers from his surgery, he finds that a recent blood test is not favorable and once again keeps his medical problem to himself.

Simone and Sipowicz investigate the murder of two roommates. Meanwhile, Medavoy investigates a story from an old friend about a man wanting to hire a hit man for a job, and he recruits Martinez for the part of playing the hit man so they can catch the crime in the act. Kirkendall and Russell investigate the claim of a wealthy woman that her maid did not accidentally donate the diamond that the woman kept in a safe place disguised as a soup can.

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.