Mycobacterium tuberculosis (Mtb), the causative agent of the disease tuberculosis (TB), is estimated to infect one-fourth of the world’s population, resulting in approximately 1.5 million deaths each year. The emergence of multidrug- and extensively drug-resistant Mtb strains and the variable efficacy of the currently used vaccine, M. bovis Bacille Calmette Guerin (BCG), are barriers to the global control of TB. Thus, there is a critical need to better understand the mechanisms of TB immunopathogenesis, as such mechanisms can be targeted to improve host control of Mtb infection. Although granulomas have long been considered a hallmark of both latent TB infection (LTBI) and clinical pulmonary TB (PTB), the immunological differences between protective granulomas and non-protective granulomas have only recently begun to emerge. Our recent data suggest that the presence of B-cell follicles in inducible bronchus-associated lymphoid tissue (iBALT)-containing granulomas is indicative of protective granulomas that mediate Mtb control during LTBI. In contrast, infiltrating neutrophils producing proinflammatory molecules are characteristic of non-protective granulomas during PTB. In this talk, Dr. Khader will challenge the current paradigm that TB granulomas are generally protective and advocate a new model for TB immunopathogenesis in which protective granulomas contain iBALT whereas non-protective granulomas are neutrophilic or exhibit immune activation.