Detective Remy McSwain is a brash, womanizing, and unconventional New Orleans police detective who doesn't always play by the rules in order to get criminals locked up. But with the help of his uncle C.D. LeBlanc, the police chief and a fanatic Civil War buff, and Remy's man-hungry detective partner, Darlene Broussard, he always manages to stay one step ahead of the law. But everything changes with the arrival of Anne Osborne, a district attorney from Washington DC whom is sent to oversee a case of illegal fishing in the remote bayous where Remy is investigating a murder which may lead to a high-up power in the city council. Anne finds herself captivated by the intense good/bad cop who tries to gain her affections with the help of his street informant and blues musician Smiley Dupree, while the local district attorney, Lightnin' Hawkins, persuades Anne to get close to Remy in order to nail him on a corruption probe the city is putting on.

As Anne settles in New Orleans (aka: The Big Easy) to stay, Remy continues to try to win her affections with the help of Smiley and his other associates, while both Anne and Remy have fantasies about the other, while Lightin' Hawkins also tries to get Anne to notice him as well. Meanwhile, a fortune-telling friend of Remy's, named Zelda Riley, tells him about a premonition about a street informant being murdered. Remy investigates and soon locks horns again with Anne who suspects Zelda somehow being involved, while Remy thinks otherwise and sets out to prove it.

Remy investigates the murder of a groom at his bachelor party where the only evidence is that of a high-heeled shoe left behind by the killer who may have been a transvestite. In attempting to dig into the past of the murder victim, Anne also learns some hidden facts about the groom's real interests as well as the bride-to-be's urges. Elsewhere, C.D. tries to find time to help Remy with his investigation while planning to hold another Civil War re-enactment outside of town.

Remy and Anne investigate the mysterious death of a jazz musician friend of Smiley's where circumstantial evidence points to supernatural occurrences connected to a shady music producer, named Tyrell, whom Remy begins to suspect that he may in fact be the Devil incarnate. But the skeptic Anne tries to put together a rational explanation for the unexplained events happening around them when a blind blues singer confirms that the musician's death was Satan's work.

Remy investigates the death of the father of a young debutante in a suspicious plane crash in the swamps and learns a series of facts about the unscrupulous businessman, including the fact that C.D. was romantically involved with the widow of the victim. Meanwhile, Anne, with Darlene's help, strikes out on her own investigation into the mysterious death by trying to establish a motive by either the debutante daughter Alana, or the estranged artist son Kent .

Anne's fiancée, Geoffrey Stodermayer, a marine biologist, arrives in town to set an upcoming date for their wedding in which Remy drags him into his latest case of investigating a shady strip club owner's liquor imports in which Geoffrey develops an attraction to Gigi, an informant who works at the Naked Angel exotic club and is soon put in jeopardy by the thugs out to silence her and anyone else who informs on them.

Remy tries to help out his old friend Delbert, a gambling addict, whom is heavily in debit to a local mobster. But when a treasury agent is found murdered at the casino boat where Delbert hangs out, Anne learns that he has been investigating Remy at the behest of Hawkins, while the leads that Remy follows point to the casino owner who is involved in a counterfeit operation and he asks Anne to pose as bait to entrap the owner.

Remy begins moonlighting as a personal bodyguard to a wealthy shipping magnate when his life is threatened. But Remy cannot resist temptation to the rich guy's young wife, Isabella, while leads point to a sordid state of affairs involving a prenuptial agreement, and the man's first jealous wife. Meanwhile, Anne asks Smiley to go undercover to investigate Isabella's past involving her shady "brother" Martin connected to a local pimp who may hold a clue to the case. Elsewhere, Darlene struggles to run the station house in the absence of several officers on leave.

When Anne's younger sister, Sophie, arrives in town for a quick visit, Remy takes them, Darlene, and Smiley out to a fund raiser at a local art gallery to save a local radio station where the star DJ, Cougan, is murdered. With everyone trapped inside the building by a sudden hurricane, Remy puts his detective skills into full force to find the killer in a building where nearly everyone, including Sophie, is a suspect as well as has ties to Cougan's sordid love life.

Remy investigates the mysterious death of a businessman whom he believes it to be the work of voodoo. While everyone, but the skeptic Anne, believes in the local voodoo superstitions, Remy sets off with Smiley to find the right culprit, while Anne decides to try out an experimentation to see if it really exists by concocting a "love potion" for Remy to notice her.

Remy, C.D., and Darlene investigate the mysterious death of a cult guru who was crushed to death by a large snake. While Anne and Remy try to seek out a dominatrix snake charmer who was seen in the company of the guru, Smiley is asked by Remy to go undercover at the religious group to find out any cult members with a background to mental instability as well as a connection to the handling of snakes.

On the night of Marti Gras, Remy finds himself held hostage at his hangout, the Blue Spot Bar, by an escaped convict, named Lyle Tillman (Silas Weir Mitchell), who seeks to prove his innocence of a murder-robbery the previous year while Lyle's very pregnant wife, Grace, holds C.D. hostage in his office at the police station as another bargaining chip leading to Darlene (stuck wearing a Little Bo Peep costume) as well as Anne (stuck in a Marie Antoinette costume) to try to help defuse the situation while Smiley finds himself the errand boy between the two standoffs while Hawkins assembles a group of SWAT men (stuck in clown costumes) to plan a brash assault on the bar in spite of the situation.

In this take on 'Rear Window' one of Anne's friends, Holly, who is recovering with a broken leg, thinks she's witnessed a murder in the apartment from across the courtyard from her apartment. Remy initially doubts Holly's story, but soon launches a personal investigation into the neighbor who is an illusionist from England who may be holding more than a few skeletons in his closet. Elsewhere, Remy makes a bet with C.D. for him stop smoking cigars for 48 hours.

Remy tries to help out Frank, an old piano-playing friend whom has a crush on a young mobster's girlfriend, and when he's accused of murdering the thug, Remy must go against all laws of ethics to try to protect his friend from a powerful mob kingpin, as well as the femme fatal Gina, who holds a dark past which may involve a mysterious killer, dressed as a clown, who comes after Remy. Meanwhile, Smiley decides to buy a new car for himself, but when Remy destroys it in attempt to fake Frank's death, Smiley wants compensation for it.

Remy investigates the murder of a traveling con artist whom may have been involved in a big scam to locate a mysterious cargo of merchandise worth millions. Assisting Remy and Anne with their case is a klutzy and accident-prone private investigator looking for clues involving another scam in which the murder victim's partner, a local grifter named Nikki whom Remy used to know, may be either conning them or is a target herself.

Remy, Anne, and C.D. are approached by a young policewoman and Civil War buff to help her investigate the murder of her friend who was allegedly trying to track down alligator poaches in the bayous. While Remy begins to think there is a connection between a bar owner who operates without a liquor license, Anne and Officer Joyce get stuck in a tree to get away from an aggressive alligator, while Joyce persuades C.D. to let her join his reenactment group. Also, Smiley tries to find more work to write while he continues his music career.

Remy and his team investigate the death of an elderly and ailing socialite at a fund-raiser where Anne and Hawkins were in attendance. Hawkins thinks that the manservant, Bernard, was responsible when the cause of death is listed as a deliberate prescription medication overdose. But Remy tries to prove Bernard's innocence and in so doing learns some disturbing facts about his real relationship with his employer and his connection to his young lawyer, Felice.

In the retrospective season final, Remy and Anne are abducted by a pair of redneck brothers whom Remy put away their serial killing eldest brother, leading to the mismatched detective and attorney trying to get away from their would-be killers by hiding out deep in the swamps where they reminisce about their happier and more harrowing times. Meanwhile, C.D. and Smiley figure out that Remy and Anne are in trouble when they go missing and try to find them before the Bill Brothers have their chance to lynch them.

While investigating the murder of a mysterious businessman at a kiddie park, Remy, Anne, and Smiley get drawn into a search for four parts of what appear to be a legendary treasure map leading to a hidden 18th Century pirate treasure in the area which is also sought after by a one-eyed Frenchman who may have a connection to the murder victims, and to a local barmaid who may know more than she knows about the treasure map.

While investigating the death of a wealthy businessman who died from a fall at a house reputed to be haunted, Remy and the team try to disapprove of the theory that the ghost of a scorned woman is behind it who shows up to murder three men every seven years. While Remy deals with a persistent female reporter, whom he once had a tryst with, Anne volunteers to go undercover at a local escort service to look for clues, while Smiley decides to moonlight at a taxi driver only to have his uncle's cab damaged by another falling victim.

Remy and Anne investigate the murder of a novelist who was researching a local vampire cult in New Orleans. While Remy tries to find the cult leader and prime suspect, Anne has a meeting of minds with a young research professor who had a dark past of his own.

The death of a band leader in a barroom brawl leads to Smiley's uncle getting arrested on suspicion of the murder. Remy agrees to help Smiley look into the case involving an Marti Gras Indian costume which goes missing from one hand to another which may be connected to a diamond smuggling ring. Smiley at the same time falls head-over-heels for a young investigator, named Corinne, whom is also searching for Smiley's uncle's missing costume.