In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ-specific manifestations of HIV-1 infection. There has been a clear step-wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ-specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ-specific manifestations, including HIV-associated nephropathy, wasting syndrome and cardiomiopathy, are a direct consequence of damage by HIV-1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV-1 organ-specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ-specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV-1-related neoplasia.