Tuberculosis is a major threat to global health, infecting a third of the world's population. In the United States, however, control of tuberculosis has been increasingly successful. Only 3.2% of the US population is estimated to have latent tuberculosis and there are only 11,000 cases annually of active disease. More than half the cases in this country occur in individuals born outside the United States. Human immunodeficiency virus coinfection is not a major factor in the United States, since only approximately 10% of cases are coinfected. Drug resistance is also uncommon in this country. Because the United States has more resources for the diagnosis, therapy, and public health control of tuberculosis than many regions of the world, and because many hospitals have more cases of clinically significant nontuberculous mycobacteria than tuberculosis, the management approaches to tuberculosis need to be quite different in this country than in other regions. The resurgence in interest in developing new tools and the investment in public health infrastructure will hopefully be sustained in the United States so that the effect of tuberculosis on the US population will continue to diminish, and these new tools and approaches can be adapted to both high and low prevalence areas to meet the global challenge.