Vocalist David Gahan created this brooding ballad with Depeche Mode's touring drummer, Christian Eigner, and keyboardist, Peter Gordeno. "They sent me this guitar line, and it had a bit of a Muscle Shoals vibe," Gahan told Rolling Stone. "It was a very different feel and I got this melody in my head."
Despite singing about it being "time to break up," Gahan did not intend it to be a breakup song. "I was watching the news on TV and I was writing through my own inability to really relate to another human being," he explained. "There must be something wrong with me, poison in my heart or whatever. So it was fun to play with that imagery, and it became more worldly – greed and lust and wanting what you want when you want it and nothing else matters. So I was breaking up with myself – trying to evolve, trying to break up with old ideas that I think are working for me but are not in actuality. Fortunately, that's not my relationship with my wife."
Depeche Mode keyboardist and guitarist Martin Gore told Rolling Stone that he considers "Poison Heart" to be the best song Gahan had ever written.