Driven by recent advances in biological science and technology, epigenetics has drawn increasing attention in recent years. Epigenetics-related enzymes could catalyze the addition or removal of a series of covalent modifications on genomic DNA, RNAi and histones, which can be applied as biomarkers and potential therapeutic targets in many diseases. A deepening understanding of epigenome and its role in cell functions and diseases has been validated in drug therapy initiatives of epigenetic alterations in drug discovery and medicinal chemistry research communities. Moreover, the approval of a quantity of small molecule-based interventions that inhibit or modulate specific epigenetic targets in a therapeutic manner proves that some of these targets are druggable by small molecules. Although the field is in its infancy, epigenetic modulators are expected to be attractive new therapeutic agents.