After Spoiler: blowing up Megaton and encountering Moira after she becomes a ghoul, one of the player's dialogue options is "Honey, you got reeeal ugly!" This is a reference to Evil Dead 3: Army of Darkness, where Ash says this to Sheila.

In the Hubris Comics building is a letter to an editor on the receptionist's computer which includes a number of comic book references.



"Mr. Moorellis" is likely the combined last-names of Alan Moore and Warren Ellis, two well known English comic book writers.
"Mr. Neptura" is a reference to the character "Marto Neptura" in the comic Promethea, which was written by Alan Moore.

Just outside of Big Town, there is a utility pole in the exact center of the game map with a unique plate that reads "TES-04."

This is a reference to The Elder Scrolls IV: Oblivion, also by Bethesda. The placing of this pole in the map center likely suggests a reference to TES IV's most notable landmark, the White Gold Tower, which is considered to be the central point of the continent of Tamriel as well as the Imperial Empire in The Elder Scrolls games.

Sally from the Mothership Zeta DLC makes references to a fictional pre-war show called 'Captain Cosmos', which itself features classic Star Trek references, such as "All systems normal, Captain!" and "Captain on the bridge!"

She also mentions a female 2nd officer, saying "Stella Skyfire reporting for duty! She's Captain Cosmos' second in command, at least for the first few episodes..."
This is in reference to the original, unaired pilot episode of Star Trek: The Original Series, "The Cage", in which Captain Pike has a female lieutenant who is second-in-command, simply referred to as "Number One". NBC rejected this pilot and requested a new pilot episode, ultimately making her role as second officer last for only one episode.

Another notable reference is the time slot 'Captain Cosmos' airs at, which was Thursdays at 8:00PM EST, according to leftover posters in the Hubris Comics building. Star Trek:ToS aired on the same day but at 8:30PM EST.

While the V.A.T.S. targeting system is an evolution of the targeted shot mechanic in earlier Fallout games, the slow-motion visuals were inspired by the Crash Mode Replays from the Burnout series. Artist Grant Struthers prototyped the V.A.T.S. camera system by filming stop-motion fight scenes with his Incredibles action figures.

The drug "Med-X" was originally just called Morphine, but in order to get a MA15+ rating in Australia by the Office of Film and Literature Classification (OFLC) board, all references to Morphine had to be changed to "Med-X". During the time there was no higher age rating (R18+) for video games, which would have meant the game could not be sold in Australia. The reason the OFLC board didn't pass the game was because of the usage of real-life drugs.

The voice of the protagonist as a baby is actually Game Director Todd Howard's son, Jake Howard.

Actress Courtney Cox, best known for playing Monica Geller from the TV sitcom "Friends", briefly worked for Bethesda in the 1980s. She (along with David Arquette, Odette Yustman, Ben Harper and the Zenimax board of directors) later helped host the Fallout 3 launch party on October 18, 2008.