RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA (dsRNA). Double-stranded RNA is commonly generated during viral replication and is considered to be a molecular pattern associated with viral infection. Our previous work demonstrated that viral infections in the fruit fly Drosophila melanogaster are countered by an antiviral RNAi response: the small interfering RNA (siRNA) pathway is the major antiviral defence mechanism in insects. Recently, another RNAi pathway was also suggested to be involved in antiviral defence, the piwi-interacting RNA (piRNA) pathway.The field of insect immunity has been largely dominated by studies on antimicrobial immunity, while antiviral immunity has received relatively little attention. Based on a combination of basic and applied science as well as bioinformatic approaches, we propose to investigate the molecular and cellular aspects underlying the immune dynamics of the antiviral response. We want to uncover fully the mechanism of antiviral RNAi in insects and its main attributes, such as memory, long-lasting immunity, specificity, and effect on the virus.The “nucleic-acid based” immune system that we are deciphering points to the concerted effort of multiple defence pathways from both partners as a new perspective in immunity and host-pathogen relationships.