Mitochondria, cellular powerhouses of eukaryotes, are known to act as central hubs for multiple signal transductions. Recent research reveals that mitochondria are involved in cellular innate antiviral immunity in vertebrates, particularly mammals. Mitochondrial-mediated antiviral immunity depends on the activation of the retinoic acid-inducible gene I (RIG-I)-like receptors signal transduction pathway and on the participation of a mitochondrial outer membrane adaptor protein, called the "mitochondrial antiviral signaling (MAVS)". In this review, we discuss unexpected discoveries that are revealing how the organelles contribute to the innate immune response against RNA viruses. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology. (C) 2012 Elsevier B.V. All rights reserved.