The show, which represents PBS Digital's first foray into scripted content, was created by Bernie Su, Brett Register, and Lon Harris.

Each episode generally consists of Frankenstein experimenting with cutting-edge medical technologies or theories, often using DeLacey or her childhood friends Eli Lavenza and Rory Clerval as subjects.

Partway through the series, the show's unseen camera operator and editor, Robert Walton, dies from a fall while adventuring in Alaska, where his body is left partially preserved in the snow.

Frankenstein, MD was announced in May 2014, in a partnership between PBS Digital Studios, the online arm of the American Public Broadcasting Service (PBS), and Pemberley Digital whose previous webseries included The Lizzie Bennet Diaries (an adaptation of Jane Austen's Pride and Prejudice) and Emma Approved (based on Austen's Emma).

[4] Victoria Frankenstein is a medical student and later doctor grappling with institutional sexism in what the creators called the "sort of a male-dominated profession"[4] of medicine.

[5] In early episodes of the show, Frankenstein neglected to wear gloves during her experiments which Su claimed was because, "real science and real-life procedures aren't sexy for entertainment".

Club, Myles McNutt felt that the fact that the show was a coproduction of PBS and Pemberley Digital was "the most exciting part" but that it was also the element "that takes the most time to negotiate in the series’ first three episodes, as the writers and the audience alike adjust to the distinct goals of the science fiction vlog webseries.