Izzo A et al. – This article discusses the perspectives from the National Institute of Health and National Institute of Allergy and Infectious Diseases (NIH/NIAD) Mycobacteria vaccine testing program for tuberculosis vaccines. The authors opined that the development of novel vaccine candidates against Mycobacterium tuberculosis infections has highlighted our limited knowledge pertaining to immune mechanisms required to kill M tuberculosis. Although induction of Th1 immunity is important, further studies are required to identify other required mechanisms. Novel vaccine formulations that recruit effector cells such as innate lymphoid cells may promote effector mechanisms including T cell and B cell–mediated immunity. Thus, identification of novel pathways for killing M tuberculosis has become critical for achieving the goal of reducing global burden of tuberculosis.