Members of the interferon regulatory factor (IRF) family are transcription factors implicated in the regulation of a variety of biological processes. Originally identified as intracellular mediators of the induction and biological activities of interferons, their central role in host resistance to pathogens has recently been confirmed by the recognition of their involvement in the regulation of gene expression in responses triggered by Toll-like receptors and other pattern recognition receptors (PRRs). Their function in regulating the development as well as the activity of hematopoietic cells puts them at the interface between innate and adaptive immune responses. IRFs also regulate cell growth and apoptosis in several cell types, thereby affecting susceptibility to and the progression of cancer. In this review the role of some members of the family more deeply involved in the differentiation of hematopoietic cells and in immune regulation is addressed, with a specific focus on T cells and dendritic cells.