The song was written and produced by Elliot Straite, AKA DJ Freeze. Straite had originally planned to feature the song on his own album, but plans changed when the members of Bell Biv DeVoe heard his demo version. "When the guys heard it, they went nuts. I didn’t think that record was going to be that big because it was a personal love letter to my ex-girlfriend at the time. It wasn’t a song at first. It was a letter. When I wrote it as a song, I let a lot of my friends hear it, and they said it was weird. After that, I put the music together. I was thinking I wasn’t going to be on the album because such heavyweights were already on it. I ended up having two songs on the album: “Poison” and “She’s Dope!”  Interestingly, Straite cites Kraftwerk as an influence on his production of Poison, as well as Latin music. In a 2015 interview with Chris Williams for the Red Bull Music Academy, Straite says, "When I made “Poison,” I was studying Kraftwerk. When I heard Kraftwerk’s Trans-Europe Express album and their “Numbers” record, it made me want to change my whole style and approach to music. It gave me the musical inspiration to do “Poison.” I’m also mixed with Black and Puerto Rican. I had uncles that played with big Latin bands like Tito Puente and Mongo Santamaria. You could hear the Latin elements in “Poison.” I wanted to bring the Latin element into that record by using timbales. When you hear them say “poison” at the end of the record? That came from Kraftwerk. It brought a futuristic element to the track as well. I didn’t want it to be a regular R&B record."
On the Billboard Hot 100 singles chart, "Poison" rose from number fifty-two to number thirty-eight in the week of April 14, 1990, and eventually peaked at number three for four consecutive weeks, beginning on June 9, 1990. The single also peaked at number one on the Hot Black Singles chart for two weeks. "Poison" became one of the most successful singles of 1990 (see 1990 in music), and was a staple on MTV and mainstream radio in the summer, spending ten weeks in the Top 10. The single peaked at number seven on the dance charts. "Poison" was certified platinum by the RIAA on June 1, 1990 for sales of over one million copies.