Interferon (IFN) regulatory factor-1 (IRF-1) was isolated by virtue of its affinity to specific DNA sequences in the IFN-β promoter that mediate virus responsiveness. IRF-1 was the first factor identified of the IRF family and was most extensively characterized at the molecular level. Also, its physiologic role in host defense against pathogens, tumor prevention, and development of the immune system was investigated in detail. Even though some of the functions first associated with IRF-1 were later found to be mediated in part or predominantly by other activators of the IRF family of transcription factors, IRF-1 has remained a central paradigm in the transcriptional regulation of the IFN response.