APOBEC3 (A3) proteins are a family of host antiviral restriction factors that potently inhibit various retroviral infections, including human immunodeficiency virus (HIV)‐1. To overcome this restriction, HIV‐1 virion infectivity factor (Vif) recruits the cellular cofactor CBFβ to assist in targeting A3 proteins to a host E3 ligase complex for polyubiquitination and subsequent proteasomal degradation. Intervention of the Vif‐A3 interactions could be a promising therapeutic strategy to facilitate A3‐mediated suppression of HIV‐1 in patients. In this structural snapshot, we review the structural features of the recently determined structure of human A3F in complex with HIV‐1 Vif and its cofactor CBFβ, discuss insights into the molecular principles of Vif‐A3 interplay during the arms race between the virus and host, and highlight the therapeutic implications. [ABSTRACT FROM AUTHOR]