The show was created by Steven Bochco, who originated the concept and brought in David E. Kelley to co-write the pilot, earning him a 'created by' credit.

Steven Bochco originally intended to end the series with a season-long arc in which Doogie becomes disillusioned with medicine and quits to become a writer, but ABC's abrupt cancellation due to low ratings prevented this storyline from being fully realized.

Neil Patrick Harris was the first actor the show's staff found who could convincingly play a teenage doctor, but ABC executives initially opposed his casting.

Because Bochco's contract required ABC to pay a huge penalty if it canceled the project, the network was forced to let him film the pilot despite disliking the casting; positive test-screening reception ultimately led ABC to greenlight the show.

Neil Patrick Harris has repeatedly parodied his Doogie Howser role, including in a Roseanne dream sequence, as Barney Stinson writing a computer diary on How I Met Your Mother, and in the Harold & Kumar films where he jokes about his time on the show.

Harris reprised a version of Doogie Howser in a sketch during the 2009 TV Land Awards and performed a full-orchestra version of the show's theme in a 2009 Saturday Night Live digital short.

Genetically engineered smart mice used in scientific research have been nicknamed 'Doogie mice' in honor of Harris's character.

In 2025, after Harris was announced as the voice of Deadpool in Marvel's Deadpool VR, Ryan Reynolds posted a promotional video parodying Doogie Howser's computer diary, with Robyn Lively (who played a recurring character on the show) also appearing.