The RIG-I-like receptor (RLR) family of cytosolic RNA sensors is crucial for eliciting innate immune defenses against a variety of viruses including influenza, SARS-CoV-2 and Zika virus. Emerging evidence suggests that RLRs also play a major role in sensing certain DNA viruses. In this seminar, I will present our research work defining the mechanisms by which RLRs are activated upon virus infection to initiate type I interferon responses. I will also present our recent work on characterizing the tactical strategies employed by viruses to escape RLR-mediated innate immunity.