Despite its high prevalence in adult populations, endodontic infections in individuals with systemic involvement, such as Human Immunodeficiency virus (HIV) infection, have been the subject of only a few studies. The aim of the present review was to answer the following questions: 1) Does highly active antiretroviral therapy (HAART) alter the clinical manifestation of endodontic infections? 2) Does HIV infection interfere in the development/repair of periradicular lesions? 3) Can HIV infection promote changes in the endodontic microbiota? Although there is plenty of information available regarding the different aspects of the endodontic infection, few studies were performed in HIV-infected individuals. Hence, the true impact of HIV infection on the clinical, immunological and microbiological aspects of the endodontic infection still needs to be clarified. In fact, it is mandatory to understand all aspects associated with endodontic infection and HIV infection in order to establish an adequate diagnosis, prognosis and endodontic treatment plan. The present review suggests that the clinical aspects of endodontic infections in HIV patients have changed with the introduction of HAART; HIV infection does not interfere in the development/repair of periradicular lesions; there is a significant difference in the endodontic microbiota found in HIV- and non-HIV-infected patients, with regard to both the prevalence and the proportion of specific microorganisms. Keywords: endodontic treatment, highly active antiretroviral therapy, HIV infection, periradicular lesions, viral load