Tuberculosis is still a leading cause of death in low-income and middle-income countries, especially those of sub-Saharan Africa where tuberculosis is an epidemic because of the increased susceptibility conferred by HIV infection. The effectiveness of the Bacille Calmette Guérin (BCG) vaccine is partial, and that of treatment of latent tuberculosis is unclear in high-incidence settings. The routine diagnostic methods that are used in many parts of the world are still very similar to those used 100 years ago. Multidrug treatment, within the context of structured, directly observed therapy, is a cost-effective control strategy. Nevertheless, the duration of treatment needed reduces its effectiveness, as does the emergence of multidrug-resistant and extensively drug-resistant disease; the latter has recently become widespread. The rapid expansion of basic, clinical, and operational research, in addition to increasing knowledge of tuberculosis, is providing new diagnostic, treatment, and preventive measures. The challenge is to apply these advances to the populations most at risk. The development of a comprehensive worldwide plan to stop tuberculosis might facilitate this process by coordinating the work of health agencies. However, massive effort, political will, and resources are needed for this plan to succeed.