The burden of human immunodeficiency virus (HIV)-related disease in sub-Saharan Africa continues to increase; providing adequate care for the huge number of people affected is a daunting task, especially given the limited resources available. Recent studies have shown that low-cost regimens can prevent some of the most important causes of HIV-related disease in African countries. Isoniazid preventive therapy can reduce the incidence of tuberculosis; priorities are to seek opportunities for implementation, to assess effectiveness under operational conditions, and to monitor its effect on resistance patterns. Cotrimoxazole was shown to be highly effective in reducing morbidity and mortality among individuals with symptomatic HIV disease in CÃ´te d'Ivoire, and should be implemented where it is likely to be of benefit. Pneumococcal polysaccharide vaccine was disappointingly ineffective among HIV-infected Ugandan adults, but newer conjugate vaccines are becoming available that should be investigated. The benefit of these preventive regimens to the individual may be modest when compared with the effect of antiretroviral therapy. However, simple preventive therapies could reach a much wider population than is immediately feasible for expensive and complex antiretroviral regimens, and thus have the potential for substantial benefit at the population level. The availability of effective and affordable regimens to prevent HIV-related disease may also encourage people to seek HIV testing, combat denial, and help overcome the sense of powerlessness in countries where the HIV epidemic has hit hardest.