In 1992, the feasibility and benefit of preventing Pneumocystis carinii pneumonia are well demonstrated in human immunodeficiency virus-infected patients. Although indications for prophylaxis are also well defined, the incidence of P carinii pneumonia remains exceedingly high. Among the two recommended agents, trimethoprim-sulfamethoxazole appears more effective but also less well tolerated than pentamidine aerosols. Large comparative trials using these agents and others such as dapsone, alone or in combination, are still ongoing; their results may offer alternatives, especially in trimethoprim-sulfamethoxazole-intolerant patients. The next step is to develop new agents or combinations in order to extend the spectrum of prophylactic strategies to other acquired immunodeficiency syndrome-related major opportunistic infections.