The concept of using Mycobacterium for cancer treatment goes back to the 19th Century. Today, bacillus Calmette-Guerin (BCG) vaccine is a well-established treatment for human bladder cancer that is arguably superior to intravesical chemotherapy for superficial disease and is commonly used as the first-line adjuvant treatment. Much has been learnt about the effects of BCG on bladder cancer and the immune system, but deeper understanding is required in order to improve its efficacy further, to be able to reliably predict responders and ultimately to adapt this most successful form of cancer immunotherapy for the treatment of other malignancies. This article summarizes the current understanding of BCG cancer immunotherapy mechanisms and discusses possible future developments.