Bipolar disorder (BD) is a multifactorial illness thought to result from an interaction between genetic susceptibility and environmental stimuli. Epigenetic mechanisms, including DNA methylation, can modulate gene expression in response to the environment, and therefore might account for part of the heritability reported for BD. This paper aims to review evidence of the potential role of DNA methylation in the pathophysiology and treatment of BD. In summary, several studies suggest that alterations in DNA methylation may play an important role in the dysregulation of gene expression in BD, and some actually suggest their potential use as biomarkers to improve diagnosis, prognosis, and assessment of response to treatment. This is also supported by reports of alterations in the levels of DNA methyltransferases in patients and in the mechanism of action of classical mood stabilizers. In this sense, targeting specific alterations in DNA methylation represents exciting new treatment possibilities for BD, and the 'plastic' characteristic of DNA methylation accounts for a promising possibility of restoring environment-induced modifications in patients. (C) 2016 Elsevier Ltd. All rights reserved.