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During the first season, the show was a relatively earnest serial drama focused on how young people come to Los Angeles to realize their dreams. Michael (Thomas Calabro) and Jane Mancini (Josie Bissett) were originally the stable couple in the apartment building, with Michael a sympathetic doctor and Jane a budding fashion designer. Their neighbors were flatmates Alison (Courtney Thorne-Smith) and Billy (Andrew Shue), who later began a love affair, and Matt Fielding (Doug Savant), a gay man who had no love life whatsoever during the first season.

Other original cast members were Rhonda (Vanessa A. Williams), an African-American aerobics instructor, and blonde, budding starlett Sandy Harling (Amy Locane). Sandy was written out after 13 episodes. Rhonda was removed after the first season. Early in the show's run, photographer Jo Reynolds (Daphne Zuniga) arrived from New York to escape her alcoholic husband. Initially tough, Jo would eventually soften some and enjoy an on-again, off-again romance with Jake.

Producers were faced with mediocre ratings and attempted to revamp the series during the first season. This was achieved mainly through the first-season arrival of former Dynasty vixen Heather Locklear as the scheming and assertive Amanda Woodward. Initially intended as a high-profile guest, Amanda was retained on the series on a permanent basis, but Locklear kept her "Special Guest Star" billing throughout the show's run. Amanda soon bought the apartment building, became a vice-president for the company where she and fellow resident Alison worked, and had affairs with many of the male characters, starting with Billy. During the first season, the show became less of an episodic series, and more of a soap opera with ongoing, interwoven stories.

Michael Mancini started cheating on Jane with the unstable Dr. Kimberly Shaw (Marcia Cross). He later divorced Jane and got engaged to Kimberly, and then had a fling with Jane's irresponsible sister Sydney (Laura Leighton). This established Michael as the beleagured cad and schemer he would remain until the end of the show. Like Michael, Sydney was presented as somewhat a chaotic schemer, often outwitted and double-crossed by others she was attempting to trick. Her various blunders forced her into various ill-advised career moves including briefly working as a stripper and as a prostitute. Ultimately, Michael was the only original character to appear through the show's entire run; Jane took a brief hiatus but returned for the final season.

The storylines began to heat up when a drunken Michael crashed the car, sending him and Kimberly tumbling down a ravine. Kimberly's angry, grieving mother sent word that her critically injured daughter had died in a medical facility in Ohio. Michael eluded potential manslaughter charges after Matt faked Michael's blood alcohol test results from the crash, and Sydney used this information to blackmail Michael into marrying her. Her plan was foiled when Kimberly re-appeared, alive and well, revealing that her mother had lied to keep Michael away. Kimberly returned as a more ruthless, dangerous unstable individual, with her sanity negatively affected by brain surgery.

Jake had numerous relationships with Melrose Place residents, including most of the female regulars (Sandy, Jo, Amanda, Sydney, Jane, Alison). He bought a bike shop, which burned down, and later bought Shooters, the Melrose gang's primary hangout spot for the first five seasons. Matt would have the fewest love affairs of any character in the series. In contrast with the numerous and steamy love scenes of all the other characters, Matt's sole kissing scene with a man was censored by FOX.

Alison and Billy were roommates before they were lovers, but they broke up, reconciled and planned a wedding set in the building's courtyard. But Alison fled their wedding after flashing back to childhood sexual abuse. Alison subsequently struggled with alcoholism and Billy, fed up, married rich brat Brooke (Kristin Davis), and the three wound up working at D&D together. Alison eventually married Brooke's father Hayley (Perry King), and Brooke and Hayley interfered with each other's marriages. Hayley eventually discovered he was financially ruined and, during a trip with Alison, he drowned after falling from his yacht. Billy broke up with Brooke, leading to her suicide attempt, followed by her accidental drowning in the building's swimming pool.

Meanwhile, Jo would give birth to a son after killing the baby's father, Reed, in self-defense. She then battled Reed's parents for custody of the child, a struggle that was complicated by Kimberly's gambit to steal the baby away from Jo. She later assists the Reeds in recovering the infant. After a shootout with her child's grandparents, Jo begrudgingly gave up the baby for adoption in order to protect it from the chaotic power play between her and the Reeds.

In 1995, Jack Wagner, known for his role as Frisco Jones on General Hospital, arrived as the charismatic and corrupt Dr. Peter Burns. Peter tormented Amanda, nearly killing her on the operating table before he was arrested. But for all his crimes, Peter was the first man to be the equal of ice queen Amanda. Sensing the chemistry, producers quickly made Wagner a contract player, and Amanda/Peter would remain a popular on-again, off-again couple for the remainder of the series.

These storylines, along with Amanda's catty one-liners, sexy-but-tough wardrobe and man-stealing helped make Melrose a guilty pleasure for many millions of viewers around the world. Within a few seasons, Amanda had hooked up with every male character (except the gay Matt Fielding) from the first five seasons. Many highly dramatic cliffhanger situations were also included in the series. The show's popularity led to a rash of similar nighttime serials about sexy, powerful women, such as Models, Inc., Savannah, Pacific Palisades, Central Park West and Sex and the City.

Kimberly endured as the love/hate of Michael's life and a formidable villain to all for several seasons. Her antics provided many jolts to the audience, such as her pulling off her wig to study her shaved, scarred head in the bathroom mirror; having her wig torn off in view of hospital staff by Matt; struggling to contain multiple personalities; learning combat skills at an intense survivalist camp; constructing a photo collage of Melrose Place residents with their eyes gouged out; and detonating four bombs in the apartment complex in the third-season cliffhanger.

The third season cliffhanger does not end with the explosion, however; the ending was quickly altered due to the bombing of the Oklahoma City Federal Building in that same month (May of 1995). After Kimberly plants the bombs, the residents of Melrose Place rush out to the courtyard, and the episode ends with Kimberly pushing the detonator button as she warns the residents that, "this isn't what it looks like...it's worse". The four explosions destroy half the apartment complex, killing one person and maiming another in an incendiary fourth-season opener.

By the fifth season, the series seemed to have peaked, with Amanda softening and Kimberly's long-running reign of terror finally running out of steam, and there was a growing consensus that the show could no longer shock or entertain viewers as it once had. Producers promised the fifth season would include more character development and less convoluted plot twists. After a season finale where Jo vacillated over leaving L.A. to join her new lover in Bosnia, the new season quickly explained that the now-absent Jo had indeed left town. Alison started a relationship with Jake, while Billy begins to pursue newcomer Samantha (Brooke Langton). A slate of other characters was introduced, such as hooker-with-a-heart-of-gold Megan (Kelly Rutherford), restauranteur Kyle (Rob Estes), his vengeful, lush-lipped wife (and Peter's sister-in-law), Taylor (Lisa Rinna), and Michael's bratty sister Jennifer (Alyssa Milano). After a brief trist with Sydney, Kyle soon took up with Amanda and, as ratings began to falter, Amanda morphed from vixen to victim, being rescued or assaulted or teary-eyed on a frequent basis.

This season also saw many enduring characters leave the series. Alison fooled Jake into thinking she had fallen off the wagon so that he would reunite with the mother of his long-lost child, and the two left town separately. After dominating storylines for several seasons Kimberly quietly died of a brain aneurysm. And at the end of the season, Samantha's jailbird father accidentally killed Sydney by running her down in a car at her wedding to Craig (David Charvet).

By the time Matt left Melrose Place at the beginning of the sixth season, he remarked that he wanted to say goodbye but "there's no one left." Indeed, more characters had to be introduced to revive the series, including violent Dr. Brett Cooper (Linden Ashby) and his seductive ex-wife, Lexi Sterling (Jamie Luner). The focal point of the season was the troubled relationship between Kyle and Amanda, who returned to her nasty ways after creating her own advertising agency. By the end of the season (the show's shortest), Craig had committed suicide and the characters of Billy, Sam, Taylor, Jennifer, and Coop departed Melrose Place.

As the seventh and final season began, residents learn that Matt, who had moved away a year earlier, was killed in a car accident on the way to a reunion dinner at Kyle's supper club. Bissett returned to the series in 1998 in a move to halt the series' downward spiral, and storylines centered on her early relationship with Michael. New characters were hurriedly drafted into the series: Ryan McBride (John Haymes Newton) and Eve Cleary (Rena Sofer), had difficulty gaining a following during this period of cast instability. Overall, the series seemed unable to handle the high number of cast changes in such a short time, and its popularity never recovered.

Amanda remained a leading character through the end of the series. Lexi Sterling (Jamie Luner) underwent a benevolent transformation from the rich, Daddy's girl to a scheming but popular super-bitch who succeeded in purchasing the Melrose Place building and starting a new agency, Sterling-Conway, which drives Amanda out of business. Meanwhile, the show paired the long-suffering Jane with Kyle (the actors were real-life spouses) and returned to the coupling of Amanda and Peter. By early 1999 FOX decided that the ratings erosion as well as the extremely high production costs —- it was said that they could have filmed an entire pilot just on Heather Locklear's salary —- warranted cancellation.

There is a real Melrose Place in West Hollywood, just east of Beverly Hills, but this is merely a short, undistinguished commercial stretch.