The reemergence of tuberculosis, including the impact of HIV infection and multidrug-resistant tuberculosis, have renewed interest in the bacille Calmette-Guerin (BCG) vaccine. During the past 7 decades, numerous studies have shown variable efficacy of BCG vaccination, ranging from 0% to 80%. The BCG vaccine is more likely to prevent disseminated forms of tuberculosis in children than pulmonary tuberculosis in adolescents or adults. Bacille Calmette-Guerin vaccination is recommended in asymptomatic children with or at risk for HIV infection, but it rarely may cause disseminated BCG infection and should not be used in persons with symptomatic HIV infection or AIDS. In healthcare workers with exposure to Mycobacterium tuberculosis, including multidrug-resistant tuberculosis, BCG vaccination generally is not recommended. Revaccination with BCG does not confer more benefit than initial vaccination, and repeat vaccinations should be discontinued. With recent advances in technology and a better understanding of the immunopathogenesis of tuberculosis, efforts to develop a more potent and specific vaccine need to be pursued. If a more effective vaccine against tuberculosis is developed, vaccination can be expected to have an additional impact on global tuberculosis control in conjunction with current strategies of case detection, treatment of disease, and preventive therapy.