Despite a fair amount of progress on understanding human immunodeficiency virus (HIV) epidemiology globally, the Middle East and North Africa (MENA) region is the only region where knowledge of the epidemic continues to be very limited, and subject to much controversy. It has been more than 25 years since the discovery of HIV, but no scientific study has provided a comprehensive data-driven synthesis of HIV/AIDS (acquired immunodeficiency syndrome) infectious spread in this region. The current report provides the first comprehensive scientific assessment and data-driven epidemiological synthesis of HIV spread in MENA since the beginning of the epidemic. It is based on a literature review and analysis of thousands of widely unrecognized publications, reports, and data sources extracted from scientific literature or collected from sources at the local, national, and regional levels. The recommendations provided here focus on key strategies related to the scope of this report and its emphasis on understanding HIV epidemiology in MENA as a whole. The recommendations are based on identifying the status of the HIV epidemic in MENA, through this synthesis, as a low HIV prevalence setting with rising concentrated epidemics among priority populations. General directions for prevention interventions as warranted by the outcome of this synthesis are also discussed briefly, but are not delineated because they are beyond the scope of this report. This report was not intended to provide intervention recommendations for each MENA country.