Epigenetics is key to understanding modulation of gene expression at specific stages and conditions in nervous system development and function. In epigenetic processes, a variety of enzymes contribute to modify chromatin with methyl, acetyl or other chemical marks, leading to repression or activation of the targeted gene without altering the original sequence. Aberrant activities of these epigenetic enzymes are implicated in many nervous system diseases, including neurodevelopmental disorders, brain cancer, neurodegenerative diseases, and mental illnesses. Thus, they have emerged as new targets for treating a variety of nervous system disorders. In this review, we briefly summarize the association between various epigenetic mechanisms and discuss recent progress in drug discovery efforts involving epigenetic regulators.