[3] Don Reo created the series, which starred Mayim Bialik as Blossom Russo, a teenager who lived with her father and two elder brothers.

Blossom Russo, an Italian-American teenager, lives with her single father Nick in a male-dominated household that includes elder brothers Tony and Joey.

In the beginning of the series, it is revealed Blossom's family is adjusting in the wake of their mother Maddy leaving to pursue her own life and career.

Nick is a session musician who is frequently between gigs and tours, Tony is a recovering alcoholic and drug addict who eventually goes on to become a paramedic, and middle sibling Joey is a stereotypical "dumb jock" known for the exaggerated delivery of his catchphrase, "Whoa!"

Blossom would frequently have fantasy sequences wherein she would receive advice from celebrities such as Mr. T, Phylicia Rashad, David Spade, ALF, Will Smith, and God (played by Don Novello).

[7] In 1988, series creator Don Reo had begun a producing partnership with Paul Junger Witt and Tony Thomas, in which the latter two were bringing his screenplays to television under the established Witt/Thomas Productions nameplate.

[9] Reo was also inspired by J. D. Salinger's The Catcher in the Rye and wanted to create a series about a wise-beyond-his-years, introspective teenage boy modeled closely after protagonist Holden Caulfield.

[10] NBC liked the screenplay, but network executive Leslie Lurie suggested that producers change the lead character to a girl[10] "because of the overabundance of coming-of-age stories with boys.

"[10] At the time Mayim Bialik filmed the pilot episode, she had recently worked on another sitcom project for Fox, entitled Molloy.

[10] NBC executives thought the depiction of an emotionally intuitive child paired alongside a super-chic father was too radical for its time; thus, Blossom has a more nuclear, conservative family dynamic in the pilot episode.

[10] Tony was going through his first drug/alcohol rehab period (in which Terry remarked that "he had a serious problem--he missed all of 1989") and had his own separate scene with Blossom in the kitchen as he gave her sage anecdotes about their lives.

[18] When NBC picked up Blossom as a regular series, Reo successfully convinced programming chief Brandon Tartikoff to allow the lead character to have the chic, divorced musician father he had originally envisioned for the project.

[7] Masur and Youngfellow's roles were recast, and Ted Wass, who had previously starred in Paul Junger Witt and Tony Thomas' 1970s sitcom Soap, was cast as Blossom's single dad Nick Russo.

[1] Bill Bixby became a frequent director on the series in its third season, a role he continued in for several episodes into the fourth, despite his ongoing battle with prostate cancer.

[19] In the pilot episode, the song in the opening credits is Bobby Brown's 1988 hit single "My Prerogative",[7] which plays as Blossom dances in her bedroom on home video.

The opening sequence for season two was changed to clips of dance moves by the title character on film and in front of a pastel blue/pink background.

The fifth and final season dropped a full-fledged intro, instead simply displaying the Blossom show logo over the watercolor effect to the opening notes of "My Opinionation".

"[12] Zurawik added that in Beverly Hills, 90210, another popular show for teens, "the boys are the main characters, and the girls come up and either create the problem or tag along.

"[10] The outfits worn by Blossom and Six turned the characters into trend setters, popularizing flowered, floppy hats,[5] baby-doll dresses, and sundresses.

[42] The show was also referenced in a 2010 episode of Glee[43] and on sitcom The Big Bang Theory,[44] the latter which Bialik joined as a main cast member.

In January 2022, the season 2 premiere of Call Me Kat, a Fox sitcom starring Bialik, featured a reunion of original Blossom actors von Oÿ, Lawrence, and Stoyanov.

[45] The trio portrayed themselves as actors from the sitcom, but did not refer to the titular character Blossom and only referenced the iconic hats and opening credit dance numbers.

Factory (under license from rights-holders ABC and Walt Disney Studios Home Entertainment) released Seasons 1 & 2 of Blossom on DVD in Region 1.

[53] Bialik told Vanity Fair, “We’re hoping to reboot it not as a sitcom, though…we want to bring back these interesting, deep characters—a child of divorce, a recovering drug addict, an alcoholic—to see them in a whole new way.”[54]