Disease in this song is a metaphor. The girl herself, or at least the feelings he has for her, is the real disease. She's bad for him, and he's trying to cure himself of her, and hopes someday to be free of her destruction.
The entire album is a timeline of a relationship. In the beginning the relationships is fine. "Disease" marks the time red flags start to show and it regresses from there, including a rebound documented in the last song.
Matchbox Twenty frontman Rob Thomas wrote this with Mick Jagger. In a 2020 Songfacts interview, Thomas recalled: "I just knew that I was going to go into the studio with one of the greatest rock star/songwriters of all time and didn't want to show up empty handed so I wrote the first verse and chorus the night before. It felt so good that he liked it but I was really happy when he decided that one song we wrote together, 'Visions Of Paradise,' was going to be on his solo album [2002's Goddess In The Doorway] but that Matchbox should do 'Disease' because he liked my voice on it."
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