Several mycobacterial species that infect and cause disease in humans are designated the Mycobacterium tuberculosis complex. This aerobic, gram-positive, acid-fast bacillus replicates largely in mononuclear phagocytic cells of the host and causes disease in lung as well as other organs. The complete genome sequences of several human and animal mycobacterial strains have been determined. More than one-third of the world’s population is infected with M. tuberculosis. Annually, 10 to 20 million of these individuals develop clinical symptoms, and about 1.7 million die of disease. The high incidence of infection is a consequence of this microbe’s stability and its facile transmission via aerosol. Over the last 2 decades, increased urbanization and immigration, as well as the immunosuppression associated with HIV infection, have contributed to the resurgence of M. tuberculosis infections and disease. Although drug therapy against the M. tuberculosis complex shows good efficacy, multi-drug resistance is now also contributing to the rise of tuberculosis in several nations. The Bacille Calmette-Guerin (BCG) live-attenuated vaccine shows poor protection from infection. Accordingly, studies at the CCM are focused on the development of the rhesus macaque model for pathogenesis and vaccine studies of M. tuberculosis. The role of colonization of macaques with Helicobacter pylori on tuberculosis disease progression is under investigation at CCM. Because of the need for rapid and accurate diagnostic methods, additional efforts are directed at using multiplex technologies to analyze host responses to M. tuberculosis exposure and infection in humans and macaques.