Exploration of the epigenome—collectively defined by DNA methylation, post-translational histone modifications, histone variants and other regulators of genome organization and function—has emerged as one of the most prolific areas of the basic and clinical neurosciences alike. This is due to a number of recent developments, including a wealth of genetic information on psychiatric disorders indicating that many risk-associated DNA variants and mutations do not affect protein coding sequences. Furthermore, the hopeful prospect of chromatin modifying drugs to lead to novel therapeutic options—while largely based on preclinical studies in small laboratory animals such as rats and mice— has infiltrated many areas of medicine, including neurology and psychiatry. Here, we summarize current concepts and emerging insights on epigenetic regulation in the nervous system, with focus on the human brain and the neurobiology and pharmacology of cognitive and emotional disease.