The innate immune system initially recognizes RNA virus infection and evokes antiviral responses by producing type I interferons (IFNs). Toll-like receptors (TLRs) and cytoplasmic retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) are the two major receptor systems for detecting RNA viruses. The RLH signaling pathways play essential roles in the recognition of RNA viruses in various cells, with the exception of plasmacytoid dendritic cells, which utilize TLRs for virus recognition. The route of infection determines the cell types responsible for type I IFN production. Recent studies have suggested that TLRs are critical for activation of adaptive immune responses against several virus infections, although it may be premature to draw such a conclusion for virus infections in general. In this review, we will discuss recent advances toward clarifying the signaling pathways activated by RLHs and TLRs.