Type I interferon (IFN) is produced in a variety of tissues in the body in response to viral infections. Recent studies have revealed that cytoplasmic receptors for viral (nonself) RNA are responsible for triggering IFN production. Different viruses activate different sensors. Numerous signaling adaptors are reported to participate in the regulation of the IFN gene's activation. In this paper, the role of free polyubiquitine chains in the activation of retinoic acid inducible gene I (RIG-I)-like receptors and the involvement of mitochondria as a signaling platform in the modulation of RIG-I-like receptor signaling is reviewed.