Background: The natural history of HIV infection has changed dramatically after theintroduction of highly active antiretroviral therapy. Currently, opportunistic illnesses stillrepresent a major cause of death and hospitalization in this population. In this study,we review the trends in opportunistic illnesses incidence rates and compare the resultsobserved in high-income settings with that for low/middle-income settings, with specialattention given to studies from Brazil.Methods: We systematically searched Pubmed, Web of Science, Lilacs and Google scholarfor publications on HIV associated opportunistic illness. Studies reporting rates based onperson-time for all opportunistic illnesses and/or the three opportunistic infections ofinterest, namely, Pneumocystis carinii pneumonia, cerebral toxoplasmosis, and Mycobacteriumavium complex were included.Results: Significant reductions in the incidence rates were demonstrated for opportunisticillnesses overall and also for the specific opportunistic infections included in the presentstudy, both in high and low/middle-income settings. Out of the 37 studies included in thepresent review, almost 70% were from high-income settings. All the studies conducted inlow/middle-income settings were single center studies and four were from Brazil. We foundno study from Brazil reporting annual incidence rates of opportunistic illnesses.Conclusions: Opportunistic illnesses remain an important public health problem. To betterguide health policies in low/middle-income settings, multicenter cohort studies should beencouraged. Studies from Brazil are urgently needed to assess the current burden of oppor-tunistic illnesses in our population and to support the planning of HIV/AIDS health careservices organization.