The most successful immunotherapeutic treatment for nonmuscle invasive bladder cancer (NMIBC) to date is the intravesical instillation of Mycobacterium bovis bacillus Calmette–Guerin (BCG). This chapter presents both the unsuccessful and the encouraging immunotherapeutic agents that can serve as substitutes for live-BCG treatment, from species of microorganisms genealogically distant from mycobacteria, such as lactic bacteria, to purified mycobacteria antigens, nonviable mycobacteria, or nontuberculous mycobacteria. It focuses on the special characteristics that make mycobacteria different from other microorganisms. The chapter describes possible future approaches to solving the problems associated with live-BCG treatment. The shortage of BCG, which has been worsened by the announcement that the main supplier to date has stopped its production, has revealed the scarcity of tools with which to treat NMIBC patients. Regardless, the availability of a nonviable immunotherapeutic agent, which carries no risk of BCG infection, would make clinicians sure of the origin of the systemic reaction.