Abstract: The HIV-1 Vif protein has been shown to counteract the antiviral activity of the cellular cytidine deaminase APOBEC3G. Based on several experimental evidences a paradigm has been established, stating that APOBEC3G is incorporated into newly formed viruses and deaminates the viral genome during the retrotranscription process following a new round of infection, leading to non-functional proviral DNA. Vif targets APOBEC3G in the virus producing cells and induces its degradation, thereby preventing its virion encapsidation. Recent findings, however, challenge this simplistic view and suggest that the biological roles of Vif and of APOBEC3G are far more complex and elusive than anticipated.