The interferons (IFNs) are a family of cytokines that elicit pleiotropic biological effects (Pestka et al. 1987; DeMaeyer and DeMaeyer-Guignard 1988; Sen and Lengyel 1992). Although best known (and named) for their ability to inhibit viral replication in treated cells, IFNs are also capable of regulating cellular proliferation, differentiation, and immunological responses (Lengyel 1982; Pestka et al. 1987; Baron et al. 1992; Vilcek and Sen 1996). Over the past 40 years, studies of IFN expression, structure, and function have provided a number of important scientific breakthroughs. The IFNs were the first cytokines to be cloned and characterized, and the first to be used therapeutically. The study of how the transcription of the IFN genes is regulated has provided insight into the complexities of inducible gene expression in eukaryotic organisms, and the analysis of IFN-induced proteins has uncovered a number of important regulators of many physiological processes. Perhaps the most far-reaching discovery to have emerged from analysis of the IFN system has been the identification of the JAK and STAT signaling components, a finding that has ushered in a new era of cytokine and growth factor signal transduction research.