Over the last decade, contributions from many groups have revealed that primate cells are endowed with divergent proteins that inhibit the replication of HIV and SIV by cell-autonomous mechanisms. Collectively, these cell-encoded proteins are called restriction factors and are characterized by a number of shared features. Specifically, restriction factors:  are often constitutively expressed, act in a dominant manner, are species-specific in that they are relatively ineffective against wild type virus strains in cells of the natural host, are frequently targeted for inhibition by virus-encoded accessory proteins, and have been subjected to positive evolutionary selection. This presentation will review the 3 major recognized HIV/SIV restriction systems of primates, namely those mediated by the APOBEC3, TRIM5a, and tetherin proteins, and the strategies exploited by HIV/SIV to evade inhibition. Importantly, various lines of experimentation have also indicated that alternative modes of restriction exist; an update on some of these recent advances will be provided.