Type I interferon (IFN-A and IFN-B) genes encode a large family of multifunctional secreted proteins involved in antiviral defence, cell growth regulation and immune activation. These cytokines, as a consequence of their biological activities, have been established as effective therapeutic molecules for malignant and viral diseases. Virus infection is the main inducer leading to transient expression of type I IFN (A and B) and the antiviral response appears to proceed through a two-step pathway requiring, first, induction of type I IFN gene expression and, second, transcriptional activation by the synthesized IFN proteins, binding to their specific cell surface receptors, of a large number of genes. The proteins they encode are responsible, in part, for the pleiotropic multiple biological activities of the IFN. In this two-step pathway, the virus-induced IFN genes and the IFN-stimulated gene (ISG) expression seem to share common factors. Even if IFN-A genes are structurally related and very often coordinately induced in virus-infected cells, differences in the expression of the individual IFN-A messenger RNAs of the multigenic IFN-A gene family are observed in human as well as in murine cells, reflecting, in a particular cell type, the transcriptional activity of the corresponding promoter regions. Important studies on interferon regulatory factors and ISG factors have been made in the last decade. However, some factors involved in IFN-A gene regulation remain to be identified. Our goal has been to review the factors involved in the control of the type I IFN gene expression to understand the mechanisms of induction and repression of their transcription and to explain the properties of these cytokines through their signal transduction pathway.