CCAAT/enhancer-binding proteins (C/EBPs) are key regulators of numerous cellular pro-cesses, including cell proliferation, differentiation, and tumorigenesis. Their biological activities require interactions with several protein partners and the formation of functional multiprotein complexes involved in DNA repair and cell cycle control. Members of the fam-ily (C/EBPα, β, δ, ε, and γ) bind to common DNA sequence motifs as homo- or hetero-dimers and interact with other transcription factors to control transcription of a number of eukary-otic genes. Of particular interest is C/EBPβ, which binds to closed chromatin and acts as a pioneering factor for initiating tissue-specific gene expression at several promoters. This review focuses on intermolecular interactions that underlie C/EBPβ’s ability to regulate chro-matin accessibility and directs readers to general reviews describing transcription regulation in eukaryotes.