c-Rel is a member of the nuclear factor κB (NF-κB) transcription factor family. Unlike other NF-κB proteins that are expressed in a variety of cell types, high levels of c-Rel expression are found primarily in B and T cells, with many c-Rel target genes involved in lymphoid cell growth and survival. In addition to c-Rel playing a major role in mammalian B and T cell function, the human c-rel gene (REL) is a susceptibility locus for certain autoimmune diseases such as arthritis, psoriasis, and celiac disease. The REL locus is also frequently altered (amplified, mutated, rearranged), and expression of REL is increased in a variety of B and T cell malignancies and, to a lesser extent, in other cancer types. Thus, agents that modulate REL activity may have therapeutic benefits for certain human cancers and chronic inflammatory diseases.