The third part of the Drosophila innate immune response is the double-stranded RNAi pathway that is involved in defending against many types of viral infections, and which also protects against viral infection in plants and animals (for a review, see Sabin et al., 2010) (Fig. 1D ). The RNAi pathway is activated by viral nucleic acids and can be broken down into two main steps: (1) biogenesis of 21-base-pair double-stranded viral small interfering RNAs (siRNAs), which is accomplished by the Dicer protein complex, and (2) the silencing of viral RNAs by the host-induced viral siRNAs, which is accomplished by the RNA-induced silencing complex (RISC). This innate protective system has been highly amenable to analysis using genome-wide screening in Drosophila cells (see below).