Abstractc‐Rel is a proto‐oncogene first identified as the cellular counterpart of the v‐Rel oncogene derived from the avian reticuloendotheliosis retrovirus (REV‐T). It was subsequently discovered that c‐Rel belongs to the NF‐κB/Rel transcription factor family whose members share a common DNA recognition motif and similar signaling pathways. Despite the similarities, however, each NF‐κB/Rel member possesses unique properties with regard to tissue expression pattern, response to receptor signals and target gene specificity. These differences are fairly evident from the non‐redundant phenotypes exhibited by (...) individual NF‐κB/Rel knockout mice. Hence the work described in this review will compare and contrast the various physiological functions of c‐Rel to those of other NF‐κB members, particularly with respect to the regulation of proliferation, survival and effector functions in multiple hematopoietic and immunological cell types. The study of c‐Rel knockout mice in several disease models will also be discussed as they reveal an important role for c‐Rel in response to allergens, auto‐antigens, allo‐antigens and pathogenic infection. BioEssays 25:767–780, 2003. © 2003 Wiley Periodicals, Inc. (shrink)