mycobacterium tuberculosis is the most prevalent infectious pathogen in the world, largely due to its unique interactions with the human immune system. Even in a normal host, a frequent outcome of infection with M. tuberculosis is failure to completely eradicate the organisms, despite the development of cell-mediated immunity. Viable organisms persist in a state in which they do not progressively replicate, leading to latent infection, which carries a risk of breakdown into active (reactivation) tuberculosis at some point later in life. Key features of the immune response against mycobacteria are reviewed here, and potential mechanisms by which the organisms may subvert these host defenses are discussed. Despite the multicellular nature of the host response to infecting mycobacteria, the organisms cannot be eradicated and contribute to the ongoing worldwide epidemic with tuberculosis.