The field of insect immunity has been largely dominated by studies on antimicrobial immunity, while antiviral immunity received relatively little attention. The discovery of RNAi as an antiviral mechanism, first in plants and later in nematodes and insects, launched a new phase in studying host-pathogen relationships and immunity. Based on a combination of basic science and bioinformatic approaches, we analyze the mechanisms underlying viral tropism, systemic propagation of the antiviral signal and the basis of the persistence of the antiviral state. Furthermore, we examine whether the antiviral RNAi response is conserved in mosquitoes and its relationship with viral immunity in that host.