The use of live M. bovis BCG to treat superficial bladder cancer has endured its seemingly anachronistic origin in the early days of tumor immunology to emerge as the therapy of choice for superficial bladder cancer. Its superiority over conventional intravesical therapy has been established for tumor prophylaxis and treatment of residual disease and CIS, providing long-term results that have translated into improvements in disease progression and survival. Although its exact mechanism of action remains elusive, extensive studies suggest that this intracellular pathogen stimulates the immune system to produce powerful cytokine mediators and effector cells that act locally to destroy bladder tumors. Although unique toxicities occur by virtue of BCG's use as a live vaccine, this same liability has opened the door for new opportunities through the use of recombinant DNA technology. Exciting prospects include the use of BCG as a cytokine carrier and as a tumor antigen depot. Genetic engineering may also yield varients that are both intrinsically safer and more specific in bladder tumor targeting.