The show was created by executive producers Dottie Dartland and Chuck Lorre, drawing much of its comedic inspiration from culture-clash, fish-out-of-water situations between its two mismatched leads.

The series' theme song was written and performed by composer Dennis C. Brown.

Jenna Elfman won the 1999 Golden Globe for Best Actress in a Musical/Comedy Series for her role as Dharma, after being nominated three times overall; Thomas Gibson and Susan Sullivan also received Golden Globe nominations but never won.

The series experienced a dramatic ratings boost in its third season after being moved to Tuesdays at 9 p.m., benefiting from a lead-in of the then hugely popular Who Wants to Be a Millionaire.

The finale aired on April 30, 2002 to 6.8 million viewers, a steep drop from the 20 million viewers the show had peaked at two years earlier.

Each episode ended with a Chuck Lorre Productions vanity card containing personal messages written by co-creator Chuck Lorre; because the card appeared only briefly, it was mostly readable only by viewers who paused their recordings, though the full collection was later posted on Lorre's website.

Jenna Elfman and Thomas Gibson made a cameo as an unnamed couple apparently based on Dharma and Greg in the season 9 premiere of Two and a Half Men, 'Nice to Meet You, Walden Schmidt,' with Joel Murray also appearing in the episode as a different character named 'Doug' rather than his Dharma & Greg role of Pete.

Jenna Elfman had earlier guest-starred on Two and a Half Men's first season as a different free-spirited character named Frankie in the two-part episodes 'Round One to the Hot Crazy Chick' and 'That Was Saliva, Alan.'