Opportunistic parasitic infections are an important cause of morbidity and mortality in people infected with HIV. Since the introduction of highly active antiretroviral therapy (HAART), there has been a marked reduction in the occurrence and clinical course of these parasitic infections. Although these changes have been attributed to the restoration of cell-mediated immunity induced by either non-nucleoside reverse transcriptase inhibitors or HIV protease inhibitors, in combination with at least two nucleoside reverse transcriptase inhibitors included in HAART, there is evidence that HIV protease inhibitors have a direct inhibitory effect on the proteases of parasites. The results of studies on opportunistic parasitic infections conducted both before and during the HAART era indicate the need to develop clinical trials on the efficacy of HIV protease inhibitors in controlling parasitic infections in individuals with HIV or other immunocompromised individuals and laboratory investigations on aspartyl proteases of parasites as an important target for the development of new drugs.