Epigenetic mechanisms integrate signals from diverse intracellular transduction cascades and in turn regulate genetic readout. Accumulating evidence has revealed that these mechanisms are critical components of ongoing physiology and function in the adult nervous system, and are essential for many cognitive processes, including learning and memory. Moreover, a number of psychiatric disorders and syndromes that involve cognitive impairments are associated with altered epigenetic function. In this review, we will examine how epigenetic mechanisms contribute to cognition, consider how changes in these mechanisms may lead to cognitive impairments in a range of disorders and discuss the potential utility of therapeutic treatments that target epigenetic machinery. Finally, we will comment on a number of caveats associated with interpreting epigenetic changes and using epigenetic treatments, and suggest future directions for research in this area that will expand our understanding of the epigenetic changes underlying cognitive disorders. © 2012 American College of Neuropsychopharmacology. All rights reserved.