The multidomain HIV-1 Vif protein recruits several cellular partners to achieve neutralization of the antiviral activity of APOBEC3 proteins. Vif neutralizes APOBEC3G and APOBEC3F predominantly by forming an E3 ubiquitin ligase with Cullin5, ElonginB and ElonginC that targets these proteins for degradation by the ubiquitin-proteasome pathway. Vif associates with the Cullin5-ElonginB-ElonginC complex by binding directly to ElonginC via its SOCS-box motif and to Cullin5 via hydrophobic residues within a zinc-binding region formed by a conserved HCCH motif. The HIV-1 Vif-Cullin5-ElonginBC complex is then able to ubiquitinate the APOBEC3G factor bound to Vif by its N-terminal domain. In this review, we summarize the current knowledge about the structural determinants of Vif that allow it to interact with cellular and viral partners.