A variety of mechanisms of innate immunity that protect organisms from retroviral infections, including HIV, are known. Lentiviruses express viral infectivity factor (Vif) protein that has the ability to counter antiviral activity exhibited by the recently discovered host cytidine deaminases APOBEC3G and 3F. Although these host factors are present in diverse mammalian species and have been shown to act against various organisms, their importance in HIV infection has been highlighted because of their suggested activities against HIV in vivo and the strong conservation of the HIV vif gene encoding the Vif protein capable of countering this innate activity. The main purpose of this review is to provide a detailed overview on HIV-specific interaction of APOBEC3 subfamily of proteins and discuss its potential role in HIV pathogenesis.