Abstract Autoimmune disease appears to be influenced by multiple factors, including the genetic, hormonal and immunological status of the individual. However, environmental agents have also been implicated in the initiation of these diseases, and mycobacteria have for a long time been listed among these agents. In this article, Yehuda Shoenfeld and David Isenberg summarize the current evidence linking mycobacterial infection with autoimmune disease. Based on considerable evidence of molecular mimicry between mycobacteria and host antigens, they postulate possible ways in which mycobacteria may precipitate autoimmune disease.