Several prominent protein antigens involved in antibody and T cell responses to mycobacteria have been identified as members of highly conserved heat shock protein families. The immunogenicity of heat shock proteins in a broad range of infections, along with the extensive sequence identity between corresponding host and pathogen homologues, and the potential for localized accumulation in response to stress stimuli, makes these antigens attractive candidates for theories of autoimmunity based on“molecular mimicry”. The 65 kilodalton (kD) heat shock protein of mycobacteria has indeed been shown to modulate the course of autoimmune disease in experimental animals, and immune responses to this and other heat shock proteins have been demonstrated in association with human autoimmune diseases. This paper provides a brief review of the immune response to mycobacterial heat shock proteins during infection and auto-immunity.