The field of host-pathogen interactions studies à la loupe how cellular and viral proteins act to either oppose or facilitate viral replication. Ever since the first discovery of the concept of viral restriction in the mid half of 1900, the field has flourished and especially so in the case of HIV-1, the virus responsible of the AIDS pandemic. This editorial is meant to provide the necessary background on the field of host-pathogen interactions in HIV replication to better appreciate two reviews that appear in this issue of Virologie on two important antiviral restriction factors: APOBEC3G and TRIM5a.