Type I interferons (IFNa/b) form a family of related cytokines that include INFa, b, e/s, j, x (human) and limitin (mouse). These cytokines exert a potent antiviral activity, control cell proliferation and modulate the immune response. They are used in the fight against viral infections, tumors, and multiple sclerosis. Expression of IFNs is typically induced by viral infections. Cells express cytoplasmic helicases as well as endosomial toll-like receptors acting as sensors to detect endogenous and exogenous viral infections, respectively. Signal transduction from these sensors induces the transcription of IFN genes. IFNs are secreted and bind to a cell surface receptor expressed by most cells of the organism. Upon receptor binding, IFNs induce the transcription of hundreds of genes whose products exert antiviral, antiproliferative and immunomodulatory functions. Antiviral activity of IFNs is so potent that most (if not all) viruses developed strategies to antagonize the IFN response.