How the hosts recognize and clear invading viruses is one of the key issues in molecular immunology. Previous studies uncovered that many early antiviral proteins, such as Type Ⅰ interferons and PKR, are strongly induced upon virus infection. These proteins not only limit virus replication and spread or cause infected cells to undergo apoptosis, but also induce consequently expression of cytokines and chemokines to initiate acquired immunity. However, the immediate-early signaling events among host and virus interaction were largely unknown. In the past few years, there are great breakthroughs in this rapidly evolving field. TLR3 and RIG-I/MDA5 signaling pathways were shown to play a crucial regulatory role in antiviral processes. These pathways are essential for the vertebrate immune system to recognize and clear RNA virus with different strategies, which are integral parts of innate immune response and directly affect later-stage acquired immunity. The recent know-how on TLR3 and RIG-I/MDA5 signal transduction pathways and their roles in antiviral immunity were summarized.