Epigenetic mechanisms of gene regulation have an important role in brain development, and evidence is accumulating that some neurological, psychiatric and behavioural disorders can be triggered or maintained by epigenetic means. In this Perspective article, Moshe Szyf explores the epigenetic basis of disorders of the central nervous system (CNS) and discusses strategies for the development of epigenetic-targeted drugs for CNS indications, as well as the particular challenges associated with this approach.