[2][3] The series follows a group of gifted students in the Individualized Honors Program (IHP) at the fictional Millard Fillmore High School in Manhattan, and their history teacher Charlie Moore (Howard Hesseman).

The program was ostensibly a vehicle for Hesseman, best known for his role as radio DJ Dr. Johnny Fever on the sitcom WKRP in Cincinnati (1978–1982).

A revival of the series was ordered and co-produced by Bill Lawrence's Doozer and Warner Horizon Scripted Television.

Alan Pinkard (Tony O'Dell) was an ultra-conservative preppy and egotist; his area of expertise was political science and he was a devout fan of Ronald Reagan.

Maria Borges (Leslie Bega) was the pretty girl, but intelligent, with some emotional and mental issues but was very passionate about getting A's (going as far as grounding herself in the pilot episode for getting a 'B'), and Jawaharlal Choudhury (Jory Husain aka Joher Coleman) was an exchange student from India whose expertise was natural science.

Eleven-year-old Janice Lazarotto (Tannis Vallely), despite her young age, was in high school and the IHP class because of her advanced intellect.

A notable development in the show was the relationship between Simone and Eric Mardian (Brian Robbins), an aspiring writer and, outwardly, the most unlikely member of the IHP.

Janice left for Harvard, Maria went to Performing Arts High School, and Jawaharlal moved to California with his family.

New students included Aristotle McKenzie (De'voreaux White), described by Dennis as "this reject from Do the Right Thing" for his dreadlocks, Viki Amory (Lara Piper), a new-ager interested in quantum physics and skin-revealing clothing, and Alex Torres (Michael DeLorenzo), who had transferred from parochial school with a love for dance and an eye for the ladies (in particular, Simone and Viki).

T.J. Jones (Rain Pryor), who had first appeared as a potential IHP member in season three, was eventually added to the program and the cast.

Appearing as regulars throughout all five seasons were school administrators Dr. Harold Samuels (William G. Schilling) the principal of Fillmore High and Bernadette Meara (Jeannetta Arnette).

Dr. Samuels distrusted the kids (and had a particularly antagonistic relationship with Dennis, and tried to avoid Eric), but at the same time he was proud of their achievements and valued the prestige they brought to the school.

Parents who appeared more than once included: Out-of-work actor Charlie Moore began the first season as a substitute teacher, but warmed to the IHP class immediately, making it his mission to get them to think rather than merely to know.

Mr. Moore also decides to put on a school production of the musical Grease, and encourages the IHP (who are initially reluctant) to participate, alongside other Fillmore students.

The class has a lot of experiences while in Moscow: Dennis and Arvid take an interest in two beautiful women, until they realise they might be KGB spies; Eric meets up with his relatives in what is a very positive experience for him; capitalist Alan has an argument with a die-hard socialist in a store (who is also on the opposing Russian academic team); Sarah and Darlene decide to record the sights and sounds of Moscow; Simone goes to put flowers on a poet's grave and meets up with a charming Russian musician; Dr. Samuels believes that his hotel room is bugged, but ends up making a fool of himself; and Charlie has a brief romance with a schoolteacher.

The episode concludes with both teams attending a concert in Gorky Park swaying to the song "Far Away Lands" (written and performed by American David Pomeranz and Russian rock star Sasha Malinin).

Several new characters took their place: Alex Torres (Michael DeLorenzo) was a Hispanic athletics student whose specialty was history, portrayed as having an eye for the ladies.

Although Alex seemed attracted to Darlene particularly, both he and Eric competed for the affection of Simone and another new IHP student, the blonde hippie Viki Amory (Lara Piper).

He insisted that the students refer to him by his first name, and although he was more rousing and less laid-back than his predecessor, he proved to be just as wise and caring (Billy also had a habit of boisterously greeting his class every morning with the phrase, "good morning, geniuses", and facetiously barking to his students to, "get out of here", when the bell rang at the end of the class.

Janice Lazarotto (from seasons one–three) returned for a guest appearance in the finale, in which T.J. is named class valedictorian and the school is closed down and demolished.

[11] In January 2021, Jorge Diaz, Dior Goodjohn, Brandon Severs, Adrian Matthew Escalona and Christa Miller joined the cast.

In 2020, it was announced that season 1 of Head of the Class would be released as a "manufacture on demand" (MOD) DVD by Warner Archive, starting on June 9, 2020.