Abstract: The MYST family of lysine acetyltransferases has been intensely studied because of its broad conservation and biological significance. In humans, there are multiple correlations between the enzymes and development and disease. In model organisms, genetic and biochemical studies have been particularly productive because of mechanistic insights they provide in defining substrate specificity, the complexes through which the enzymes function, and the sites of their activity within the genome. Established and emerging data from yeast reveal roles for the three MYST enzymes in diverse chromosomal functions. In particular, recent studies help explain how MYST complexes coordinate with other modifiers, the histone variant H2A.Z, and remodeling complexes to demarcate silent and active chromosomal domains, facilitate transcription, and enable repair of DNA damage.