The type I interferons (IFN) are cytokines produced by mammalian cells in response to virus infection or other stressors. IFNs exert antiviral function by binding to the IFNalpha/beta receptors on the cell surface, with the major effect of triggering the JAK-STAT signaling cascade and inducing the expression of interferon-stimulated genes. The resulting innate antiviral response is a first line of immune defense against virus infection. Recent studies demonstrate that many viruses, including hepatitis C virus, direct processes to control the host response to infection. We provide a review of the virus/host processes involved in IFN signaling and regulation of innate immune defenses.