The interferons (IFNs) are a pleiotropic family of cytokines that perform fundamental functions in protecting host organisms from disease and in maintaining homeostasis. Like other multifunctional cytokines, excessive or inappropriate activity can cause toxicity and even death. Therefore, host organisms have evolved specific and highly regulated mechanisms to control the temporal and tissue specificity of production of IFNs and the selection of pathways and genes to be activated as the effectors of the IFN response in cells. There are now numerous microarray datasets available to enable a global analysis of the genes involved in the IFN response. This article describes the INTERFEROME database, which assimilates the available expression profiling data and its contents and enables the definition of IFN-regulated genes, discovery of pathways, regulatory networks, and tissue specificities of the IFN response.