Potent antiretroviral therapy has improved the outcome of HIV-associated OIs, which have declined dramatically. The clinical manifestations of some OIs (e.g., CMV retinitis, MAC infection, and TB) have changed. These effects likely are related to the immune reconstitution observed with the suppression of HIV replication. These changes have affected approaches to the prophylaxis of OIs. Withdrawal of some prophylaxis in patients who show evidence of immune reconstitution is possible, although clinical studies are needed to address further specific questions about the timing of withdrawal. The best way to prevent OIs is to give effective antiretroviral therapy - the future epidemiology of OIs is linked inextricably with the effectiveness of future antiretroviral treatments.