In the late 1980s and early 1990s, after decades of decline, the incidence of tuberculosis began to rise in New York city, reaching a peak of 3811 cases by 1992. The epidemic took root in a setting of inadequate treatment regimens, homelessness, a diminished public-health system, and the onset of the HIV/AIDS epidemic. In addition, a subepidemic of drug-resistant tuberculosis occurred throughout New York city, most notably in a series of well documented nosocomial outbreaks. By 1994, using broadened initial treatment regimens, directly observed therapy, and improved US Centers for Disease Control and Prevention guidelines for hospital control and disease prevention, New York city began to effectively halt the progression of the epidemic. By 2002, tuberculosis rates in New York city reached an historic low of 1084. However, given the presence of a large reservoir of latently infected individuals in the city and an ongoing tuberculosis pandemic, New York city continues to face significant challenges from this persistent pathogen.