Approximately one third of the world's population, including more than 11 million persons in the United States, is latently infected with Mycobacterium tuberculosis. Although most cases of tuberculosis in the United States occur in foreign-born persons from endemic countries, the prevalence is generally greater in economically disadvantaged populations and in persons with immunosuppressive conditions. Delays in detection and treatment allow for greater transmission of the infection. Compared with the traditional tuberculin skin test and acid-fast bacilli smear, newer interferon-gamma release assays and nucleic acid amplification assays lead to more rapid and specific detection of M. tuberculosis infection and active disease, respectively. Nine months of isoniazid therapy is the treatment of choice for most patients with latent tuberculosis infection. When active tuberculosis is identified, combination therapy with isoniazid, rifampin, pyrazinamide, and ethambutol should be promptly initiated for a two-month "intensive phase," and in most cases, followed by isoniazid and a rifamycin product for a four- to seven-month "continuation phase." Directly observed therapy should be used. Although currently limited in the United States, multidrug-resistant and extensively drug-resistant strains of tuberculosis are increasingly recognized in many countries, reaffirming the need for prompt diagnosis and adequate treatment strategies. Similarly, care of persons coinfected with human immunodeficiency virus and tuberculosis poses additional challenges, including drug interactions and immune reconstitution inflammatory syndrome.