Interferons represent a family of cytokines, which is of central importance in the innate immune response to virus infections. All interferons act as secreted ligands of specific cell surface receptors, eliciting the transcription of hundreds of interferon-stimulated genes whose protein products have antiviral activity, as well as antimicrobial, antiproliferative/antitumor, and immunomodulatory effects. Expression of type I and III interferons is induced in virtually all cell types upon recognition of viral molecular patterns, especially nucleic acids, by cytoplasmic and endosomal receptors, whereas type II interferon is induced by cytokines such as IL-12, and its expression is restricted to immune cells such as T cells and NK cells. The effectiveness of the interferon system in counteracting viral infections is reflected by the multitude of inhibitors of interferon induction or interferon action that are encoded by many viruses, preventing their eradication and resulting in the continued coexistence of viruses and vertebrates. The unique biological functions of interferons have led to their therapeutic use in the treatment of diseases such as hepatitis, multiple sclerosis, and certain leukemias. © 2009 International Union of Biochemistry and Molecular Biology, Inc.