Keeping with the theme of powerlessness of "Master of Puppets", the lyrics portray one being trapped in insanity, or perhaps incarcerated in a mental asylum. However, a sanitarium is usually a facility for treating tuberculosis and other chronic disease. It begins slowly with harmonics, which in the song are meant to simulate time slowly ticking by. This eventually leads into the main riff followed by the bass guitar, drums and solo. The lyrics progress and become more harsh as time moves on, backed by harsher vocals (in comparison to the cleaner vocals of the song) and heavily distorted guitars. The song ends with several solos and a few lyrics that hint about an uprising in the asylum. Altogether, the song is guided by powerful and moving riffs that give the song a cold and gloomy atmosphere.
The original demo version of this song features an extended ending which is eventually used as bass and guitar solos in the song "Orion".
The section of the song that begins at 4:06 ("Fear of living on/Natives getting restless now...") bears a resemblance to a main riff in the Rush song "Tom Sawyer." Metallica thanks Rush in the liner notes for the album, so the riff may have been an intentional tribute, but it has not been confirmed by either band. The song is sometimes combined with "Master of Puppets" in concert; the combination is known as "Mastertarium".
This song is also featured as background music for the film Paradise Lost: The Child Murders at Robin Hood Hills, which details the controversial West Memphis Three murder case, as the three boys listened to heavy metal.