The regulation of transcription in eukaryotes relies upon the histone proteins in several essential ways. The incorporation of the binding sites for the basal transcriptional machinery into nucleosomes serves to repress transcription. Specific regulatory molecules other than the basal transcriptional machinery exist that can associate with nucleosomal DNA and initiate a chain of events that disrupt repressive histone-DNA complexes. The main players in this story have been defined physically and genetically and include positioned nucleosomes, interactions of the histone tetramer (H3-H4)2 with DNA, the N-terminal tails of histones H3 and H4, and a large general activator complex. How they fit together biochemically is yet to be defined. The genetic data demonstrate that the disruption of histone-DNA complexes plays a major role in the induction of transcription from many genes. However, not all genes are repressed by nucleosome assembly: certain promoters make use of the staged assembly of chromatin in vivo and a rapid and tight association of transacting factors with promoter elements to remain constitutively active. Moreover, nucleosome assembly is not necessarily repressive, since the folding of DNA by the histones can facilitate the activation of genes by bringing widely separated regulatory elements into juxtaposition. Thus, histones provide the necessary infrastructure for the correct and efficient operation of the transcriptional machinery; however, their exact contributions to the transcriptional regulation of an individual gene may depend on the spatial distribution of regulatory elements, the transcription factors involved, and the three-dimensional folding of DNA that they direct.