The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia ¿PCP, esophageal candidiasis, and disseminated Mycobacterium avium complex ¿MAC disease) were more pronounced in 1996-1998, during which time highly active antiretroviral therapy (HAART) was introduced into medical care. Those OIs that continue to occur do so at low CD4+ T lymphocyte counts, and persons whose CD4+ counts have increased in response to HAART are at low risk for OIs, a circumstance that suggests a high degree of immune reconstitution associated with HAART. PCP, the most common serious OI, continues to occur primarily in persons not previously receiving medical care. The most profound effect on survival of patients with AIDS is conferred by HAART, but specific OI prevention measures (prophylaxis against PCP and MAC and vaccination against Streptococcus pneumoniae) are associated with a survival benefit, even when they coincide with the administration of HAART. Continued monitoring of incidence trends and detection of new syndromes associated with HAART are important priorities in the HAART era.