Antigen-specific gammadelta T cells may play a role in anti-mycobacterial immunity. Studies done in humans and animal models have demonstrated complex patterns of gammadelta T cell immune responses during early mycobacterial infections and chronic tuberculosis. Recent studies have also shown a clinical correlation between major recall expansion of antigen-specific gammadelta T cells and immunity against fatal early mycobacterial diseases. Multiple host and microbial factors can regulate diverse immune responses of phosphoantigen-specific gammadelta T cells during mycobacterial infections.