Possessing a genius intellect and a photographic memory,[3] Howser participates in a longitudinal study of child prodigies until his 18th birthday.

As a newspaper article (one of several noting some of Doogie's aforementioned accomplishments that are shown in the series' opening title sequence) stated, he "can't buy beer... [but] can prescribe drugs".

The series begins on Howser's 16th birthday; the cold open of the pilot episode shows him stopping his field test for his driver's license to help an injured person at the scene of a traffic accident.

His best friend and neighbor, Vinnie Delpino (Max Casella), is a more typical teenager—climbing through Howser's bedroom window to visit—and connects him to life outside of medicine.

Many episodes also deal with wider social problems: AIDS awareness, racism, antisemitism, homophobia, sexism, gang violence, access to quality medical care, and losing one's virginity are topics, along with aging, body issues, and friendship.

Howser initially has a girlfriend, Wanda Plenn (Lisa Dean Ryan), but they break up after she leaves for college; he also begins a trauma surgery fellowship and moves into his own apartment.

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

Bochco's contract required that the network pay an "enormous" penalty if it canceled the project, so ABC was forced to let him film the pilot.

The network still opposed Harris's casting and disliked the pilot, but after positive reception during test screenings, ABC greenlit the show.

"[32] Scott Weinberg of DVD Talk recommended season two: "It's not high art, but it's a heckuva lot better than what generally passes for your average weeknight sitcom.