The incidence of tuberculosis (TB) in patients with human immunodeficiency virus (HIV) infection has increased in recent years, raising issues regarding preventive therapy for TB in this high-risk patient population. To determine if an HIV-positive individual is at risk for reactivation of latent infection, testing with purified protein derivative (PPD) is recommended; however, many people with impaired cell-mediated immunity due to HIV are anergic. Strategies regarding PPD testing and criteria for HIV-positive patients are presented. Isoniazid has been the accepted drug for use as prophylaxis for TB in immunocompetent patients, and there is evidence that isoniazid is also effective in HIV-positive, PPD-positive patients. Data from efficacy and feasibility trials and the risks and benefits of preventive therapy with isoniazid are discussed. Because of toxicity and compliance problems with isoniazid, there is a continuing need for development of alternative therapies. The results of some preliminary studies of newer therapies are presented here.