Almost one third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. Each year there are eight million new cases of tuberculosis and three million deaths from the disease worldwide. Mtb is an intracellular pathogen that resides predominantly within macrophages. Paradoxically, macrophages also represent the first line of defense against this pathogen. Significant recent advances have been made in understanding the mechanisms by which Mtb gains entry into the macrophage, suppresses the microbicidal activities of this host cell, and ultimately subverts cell-mediated immune responses that eradicate the infection. This article reviews recent findings that contribute to our understanding of the roles played by mononuclear phagocytes in the immune response against tuberculosis.