This review summarizes the latest discoveries in innate immune responses to RNA, focusing on the sensing and signaling mechanisms. RNA is a critical component of the innate immune system, with various sensors recognizing RNA to trigger immune responses against pathogens, cellular stress, and cancer. Key RNA sensors include RIG-I, MDA5, TLR3/7/8, OAS1, PKR, NLRP1/6, and ZBP1, which recognize different forms of RNA and activate signaling pathways that lead to antiviral and antitumor immunity. These pathways are tightly regulated to maintain immune homeostasis and prevent autoimmune disorders. Recent advances have highlighted the potential clinical applications of targeting these signaling pathways. The review discusses the activation and regulatory mechanisms of RNA-sensing pathways, the role of RNA in immune homeostasis, and the importance of RNA sensing in disease. It also explores the evolution of RNA-sensing mechanisms across different organisms and the role of phase separation in regulating RNA sensing. The review concludes that RNA-sensing pathways are essential for antiviral immunity and that further research is needed to fully understand their mechanisms and potential therapeutic applications.This review summarizes the latest discoveries in innate immune responses to RNA, focusing on the sensing and signaling mechanisms. RNA is a critical component of the innate immune system, with various sensors recognizing RNA to trigger immune responses against pathogens, cellular stress, and cancer. Key RNA sensors include RIG-I, MDA5, TLR3/7/8, OAS1, PKR, NLRP1/6, and ZBP1, which recognize different forms of RNA and activate signaling pathways that lead to antiviral and antitumor immunity. These pathways are tightly regulated to maintain immune homeostasis and prevent autoimmune disorders. Recent advances have highlighted the potential clinical applications of targeting these signaling pathways. The review discusses the activation and regulatory mechanisms of RNA-sensing pathways, the role of RNA in immune homeostasis, and the importance of RNA sensing in disease. It also explores the evolution of RNA-sensing mechanisms across different organisms and the role of phase separation in regulating RNA sensing. The review concludes that RNA-sensing pathways are essential for antiviral immunity and that further research is needed to fully understand their mechanisms and potential therapeutic applications.