Potent antiretroviral treatment is associated with dramatic improvements in immune function in many human immunodeficiency virus-infected patients. This has led to new US Public Health Service/Infectious Diseases Society of America guidelines that suggest that in certain circumstances (primary prophylaxis for Pneumocystis carinii pneumonia and disseminated Mycobacterium avium complex infection, and secondary prophylaxis for cytomegalovirus retinitis), antimicrobial prophylaxis can be discontinued for patients whose CD4 T-cell counts rise above threshold levels for at least 3-6 months. The new guidelines are probably too conservative, and effective antiretroviral treatment almost certainly provides protection against all major opportunistic pathogens. Therefore, in the future, specific prophylaxis will be needed only for those patients who do not benefit from or fail to adhere to the current more effective treatment of human immunodeficiency virus infection.