Tuberculosis is an infectious disease caused by bacteria in the Mycobacterium tuberculosis complex. Of these, the most common species to infect humans is M. tuberculosis. The TB bacillus is an extremely successful human pathogen, infecting two billion persons worldwide; an estimated 2 to 3 million people die from tuberculosis each year. In the United States, TB rates decreased steadily at the rate of 5% per year from 1953 until 1985 when the trend reversed, with the number of TB cases peaking in 1992. Outbreaks of multidrug-resistant TB (MDR TB) were reported, and these cases were documented to be transmitted in nosocomial and congregate settings, including hospitals and prisons. AIDS patients infected with M. tb developed disease rapidly, and case-fatality rates of >80% were noted in those infected with multidrug-resistant M. tb. Intensive intervention, at enormous cost, caused the number of TB cases to decline. This article discusses factors that led to the increase in TB cases, their subsequent decline, and measures needed in the future if TB is to be eliminated in the United States.