[8] In the liner notes for Once in a Lifetime: The Best of Talking Heads (1992), Jerry Harrison wrote of the B-side of the single, "I'm glad we persuaded Tony [Bongiovi] and Lance [Quinn] that the version with the cellos shouldn't be the only one."

Originally written and performed as a ballad,[10] "Psycho Killer" became what AllMusic calls a "deceptively funky new wave/no wave song" with "an insistent rhythm, and one of the most memorable, driving basslines in rock & roll.

[13][14] Although the band always insisted that the song had no inspiration from the notorious events, the single's release date was "eerily timely"[12] and marked by a "macabre synchronicity".

[14] According to the preliminary lyric sheets copied onto the 2006 remaster of Talking Heads: 77, the song started off as a semi-narrative of the killer actually committing murders.

In the liner notes of Once in a Lifetime: The Best of Talking Heads, David Byrne says: When I started writing this (I got help later), I imagined Alice Cooper doing a Randy Newman–type ballad.

The song has been recorded in cover versions by many bands and musicians including Velvet Revolver,[25] James Hall,[26] the Bobs (a cappella group),[27] Victoria Vox,[28] Wet Leg,[29] Duran Duran featuring Victoria De Angelis,[30] Miley Cyrus,[31][32] and the Ukulele Orchestra of Great Britain at the 2009 BBC Proms.

[33] Massachusetts-based band the Fools parodied the song and entitled it "Psycho Chicken"; it was included as a bonus record with their major-label debut album Sold Out in 1980.