Abstract Over the last few decades, considerable progress has been achieved in understanding the aetiology of mental illness and its biological underpinnings. Genetic factors have been shown to play a substantial role, although genetics alone are not able to explain fully the heritability of these diseases. Epigenetic mechanisms, such as DNA methylation, histone modifications, and RNA interference, modulate tissue-specific gene expression and have been proven to be involved in the aetiopathogenesis of psychiatric disorders. Numerous epidemiological studies have confirmed a contribution of environmental factors, and convincing evidence suggests that socio-economic status, early life stressors, and childhood trauma impact significantly on the risk of psychiatric disorders via lifelong epigenetic modifications. This chapter will discuss in detail the different epigenetic mechanisms underlying the pathogenesis of psychiatric diseases and their interaction with genetic factors, providing an overall picture about the recent advances in psychiatric epigenomics.