Transcription in eukaryotes is frequently regulated by a mechanism termed combinatorial control, whereby several different proteins must bind DNA in concert to achieve appropriate regulation of the downstream gene. X-ray crystallographic studies of multiprotein complexes bound to DNA have been carried out to investigate the molecular determinants of complex assembly and DNA binding. This work has provided important insights into the specific protein-protein and protein-DNA interactions that govern the assembly of multiprotein regulatory complexes. The results of these studies are reviewed here, and the general insights into the mechanism of combinatorial gene regulation are discussed.