Post-translational acetylation of the core histone amino-terminal tails has long been associated with both chromatin assembly and the regulation of gene expression. The recent identification and cloning of histone acetyltransferase genes represents a significant breakthrough in our understanding of how specific acetylation states are established. Ongoing characterization of these enzymes and their molecular cohorts supports a direct role for acetylation in a signaling pathway that modulates chromatin structure to create new patterns of transcription.