Members of the interferon-regulatory factor (IRF) proteins family were originally identified as transcriptional regulators of the Type I interferon system. Thanks to consistent advances made in our understanding of the immunobiology of innate receptors, it is now clear that several IRFs are critical for the elicitation of innate pattern recognition receptors, and-as a consequence-for adaptive immunity. In addition, IRFs have attracted great attentions as they modulate cellular responses that are involved in tumorigenesis. The regulation of oncogenesis by IRFs has important implications for understanding the host susceptibility to several Types of cancers, their progression, as well as the potential for therapeutic interventions.