A unique feature of Mycobacterium tuberculosis is its ability to exist in the granuloma of an asymptomatic host in a latent state that can subsequently reactivate to cause active disease. The latent state of infection poses a major obstacle to eradicating tuberculosis. In latent tuberculosis, the host immune response is capable of controlling the infection and yet falls short of eradicating the pathogen. That the host immune response contributes to the maintenance of latent tuberculous infection is supported by the observation that certain immunodeficient states, including those associated with the human immunodeficiency virus and tumor necrosis factor neutralization therapy, are associated with increased risks for developing reactivation disease. Latent tuberculosis is the product of a complex set of interactions between M. tuberculosis and the host immune response. The molecular basis for the persistence phenotype of M. Tuberculosis and the pertinent host immune mechanisms that contribute to the maintenance of tuberculous latency are just beginning to be understood. This review discusses the interactions between M. tuberculosis and the macrophage, the primary host cell that the tubercle bacillus parasitizes.