Recently, the mechanisms underlying epigenetic dysregulation associated with neurodevelopmental disorders have attracted increasing attention. Although most neurodevelopmental disorders in humans are multifaceted and encompass a wide range of symptoms, a small number of cases linked to specific single gene disruptions have been identified. The Drosophila genetic system provides excellent models for such diseases. This review will discuss recent advances in the study of human neurodevelopmental disorders associated with epigenetic dysregulation, particularly monogenic disorders established in relevant Drosophila models. Due to the vast range of genes affecting epigenetic dysregulation, we aim to provide a selective review of the disorders caused by aberrant histone modifications, with particular emphasis on enzymes regulating histone acetylation and methylation, in order to give the essential understanding of the nature of the neurodevelopmental disorders for rational therapeutic treatments.