The distribution of HIV-1 subtypes in a population tracks the spread and evolution of the epidemic. This study is a systematic review of all available evidence on HIV-1 molecular epidemiology and subtype distribution in the Middle East and North Africa. Sources of data included Medline and various institutional documents and databases. In several countries, a diverse distribution of HIV-1 subtypes was observed principally reflecting travel-related exogenous exposures. A trend for a dominant HIV-1 subtype was observed in a few other settings and was often linked to HIV transmission within specific high-risk groups such as subtype A and CRF35_AD among injecting drug users and subtype C among commercial sex networks. Multiple exogenous introductions of HIV-1 variants seemed common to all countries, as observed from the high diversity in subtypes, or the high genetic divergence among any specific subtype even if predominant. In several countries though, epidemic-type clustering of specific subtypes suggests established or nascent HIV epidemics among classic core risk groups for HIV infection. HIV prevention efforts in MENA must be prioritized for these high-risk groups.