CCAAT/enhancer-binding proteins (C/EBPs) comprise a family of transcription factors that are critical for normal cellular differentiation and function in a variety of tissues. The prototypic C/EBP is a modular protein, consisting of an activation domain, a dimerization bZIP region, and a DNA-binding domain. All family members share the highly conserved dimerization domain, required for DNA binding, by which they form homo- and heterodimers with other family members. C/EBPs are least conserved in their activation domains and vary from strong activators to dominant negative repressors. The pleiotropic effects of C/EBPs are in part because of tissue- and stage-specific expression. Dimerization of different C/EBP proteins precisely modulates transcriptional activity of target genes. Recent work with mice deficient in specific C/EBPs underscores the effects of these factors in tissue development, function, and response to injury.