Summary Bacillus Calmette-Guerin (BCG) vaccines are attenuated live strains of Mycobacterium bovis and are among the most widely used vaccines in the world. BCG is proven effective in preventing severe infant meningitis and miliary tuberculosis. Intravesical instillation of BCG is also a standard treatment for non-muscle invasive bladder cancer. In the past few decades, recombinant BCG (rBCG) technology had been extensively applied to develop vaccine candidates against a variety of infectious diseases, including bacterial, viral, and parasite infections, and to improve the efficacy of BCG in bladder cancer therapy. This review is intended to show the vast applications of BCG and rBCG in prevention of infectious diseases and in cancer immunotherapy, with a special emphasis on recent approaches and trends on both pre-clinical and clinical levels.