The highly active antiretroviral therapy (HAART) era began in 1996 when the combination of multiple antiretroviral agents was found to improve outcomes in HIV-infected patients. HAART has made a tremendous impact on the progression of HIV and on the morbidity and mortality associated with its opportunistic infections. HIV-positive patients who respond to HAART have a decreased incidence of opportunistic infections. Studies have documented close to a 50% decline in the incidence of pneumocystis pneumonia and bacterial pneumonia with the use of antiretroviral therapy. Primary and secondary prophylaxis for pneumocystis pneumonia can be discontinued in patients who show a sustained response to antiretroviral therapy. Unique to the HAART era, immune reconstitution syndrome is characterized by a paradoxical deterioration of a preexisting infection that is temporally related to the recovery of the immune system. Recently, more and more patients are being admitted for non-AIDS related illnesses in the HAART era.