Schizophrenia is a severe and complex psychiatric condition ranking among the top 15 leading causes of disability worldwide. Despite the well-established heritability component, a complex interplay between genetic and environmental risk factors plays a key role in the development of schizophrenia and psychotic disorders in general. This chapter covers all the clinical evidence showing how the analysis of the epigenetic modulation in schizophrenia might be relevant to understand the pathogenesis of schizophrenia as well as potentially useful to develop new pharmacotherapies.