Madhouse was released as the only single and third track from the group's second album, Spreading the Disease. The song is written in an up-tempo time signature, with heavy distorted guitar riffs.
It has become a staple of live concerts, and has also appeared on Anthrax's "best of" album, Anthrology: No Hit Wonders (1985-1991). In 2009, the track was named the 46th best hard rock song of all time by VH1.
A music video was produced, which features the band performing in an insane asylum with several mental patients moving along to the tune. However, the video did not receive much airplay because it was banned from MTV, who believed the content to be degrading to the mentally ill.