The lentiviruses, including HIV-1 (but excluding equine infectious anemia virus), encode a viral infectivity factor (Vif) protein. Circumstantial evidence suggested that Vif acts to neutralize an inhibitory host defense mechanism, but progress in the field was limited because the identity of the cellular target was unknown. The recent identification of the elusive host cell factor let loose a flood of advances. These findings have revealed a novel innate defense mechanism against retroviruses. In infected cells, the cellular cytidine deaminase APOBEC3G, a relative of the activation-induced deaminase (AID), is encapsidated into assembling virions. The enzyme lies in the virion, waiting to wreak havoc on the viral genome in the next round of virus replication--unless it is first caught by Vif.