The host responds to virus infection by triggering various antiviral defense mechanisms, many of which are initiated by double‑stranded (ds) RNA, which is often produced in virus‑infected cells. Surprisingly, similar responses are also triggered by cellular dsRNA produced by necrotic, or otherwise stressed, uninfected cells; in human and mouse, such responses have been genetically linked to protection against several diseases of non‑viral etiology. Thus, dsRNA has a wide role in mediating host defense. DsRNA is recognized, in the cell, by a large family of dsRNA‑binding proteins, some of which share similar structural motifs that mediate the binding. Functionally, some of these proteins are dsRNA‑dependent enzymes while others are signaling receptors that trigger transcription of a cohort of cellular genes, many of which encode antiviral proteins.