Tuberculosis poses a significant threat to mankind. Multidrug-resistant strains are on the rise, and Mycobacterium tuberculosis infection is often associated with human immunodeficiency virus infection. Satisfactory control of tuberculosis can only be achieved using a highly efficacious vaccine. Tuberculosis is particularly challenging for the immune system. The intracellular location of the pathogen shields it from antibodies, and a variety of T-cell subpopulations must be activated to challenge the bacterium's resistance to antibacterial defence mechanisms. A clear understanding of the immune responses that control the pathogen will be important for achieving optimal immunity, and information provided by functional genome analysis of M. tuberculosis will be vital in the design of a future vaccine.