The mitochondrial antiviral signaling adaptor, MAVS, also known as Cardif, VISA or IPS1, is critical for host defenses against viral infection by inducing expression of type-1 interferons (IFN-Ⅰ). The sensors of antiviral immunity, RIG-Ⅰ and melanoma differentiation-associated gene 5 (MDA5), detect the invasion pathogens, and pass the signal to MAVS, which is anchored to the mitochondrial membrane. MAVS then stimulates TBK1 and IKK complex and activates the transcription factors of IRF3/7 and NF-κB, which lead to the expression of interferon and activate antiviral innate immunity. MAVS was recently found to localize in both peroxisome and mitochondrial membrane. The peroxisomal MAVS is required for the rapid induction of antiviral effectors, whereas the mitochondrial MAVS is required for a sustained antiviral immunity response. This review focused on the discovery, domain structure and cellular localization of MAVS with an emphasis on the regulatory mechanisms of MAVS in modulating the antiviral innate immunity.