Abstract: The "chromogenome" is defined as the structural and functional status of the genome at any given moment within a eukaryotic cell. This article focuses on recently uncovered relationships between histone chaperones, post-translational acetylation of histones, and modulation of the chromogenome. We emphasize those chaperones that function in a replication-independent manner, and for which three-dimensional structural information has been obtained. The emerging links between histone acetylation and chaperone function in both yeast and higher metazoans are discussed, including the importance of nucleosome-free regions. We close by posing many questions pertaining to how the coupled action of histone chaperones and acetylation influences chromogenome structure and function. J. Cell. Physiol. (c) 2010 Wiley-Liss, Inc.