Ghostbusters is a modified version of an unreleased game called Car Wars. According to the game's developer David Crane in a 2010 interview, Car Wars was "a game about buying cars, tricking them out, and dueling them against other cars around a fictional city." After one month of development, Activision co-founder Gary Kitchen called and met with him to discuss making a game based on the then-upcoming Ghostbusters film to release on the same day as the film, and Crane immediately devised a way to change Car Wars into a Ghostbusters game with only minor changes and additions.

There was a glitch in the stairway level wherein, by getting hit by a ghost hidden behind a door when you are on your last life, you can no longer be damaged by ghosts that don't come out of doors.

In the Japanese version, it's possible to earn enough money to enter the ZUUL Building early by buying and selling the Ghost Alarm over and over again as its purchase price is lower than its resale value. This glitch is fixed in the International Release.

At the ending screen, "congratulation" is misspelled "conglaturation", and "proved" is misspelled "prooved".

Due to various programming bugs in the NES version, such as the game trying to read the ending text from the wrong CHR-ROM page, the Japanese version of the game doesn't show the ending screen and credits at the end of the game.

Instead, it only shows a black screen, followed by the text "りり" (riri) scrolling onto it.