The recognition of viral nucleic acids with pattern recognition receptors (PRRs) is the first step in inducing the innate immune system. Type I interferons (IFNs), central mediators in antiviral innate immunity, along with other cytokines and chemokines, disrupt virus replication. Recent studies indicated at least two distinct pathways for the induction of type I IFN by viral infection. Toll-like receptors (TLRs) are extracellular or endosomal PRRs for microbial pathogens, whereas retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are novel intracellular PRRs for the viral dsRNA. In this review, we describe the distinct mechanisms inducing type I IFNs through TLRs and RIG-I/MDA5 pathways.