Abstract: Heart failure is the terminated stage of most kinds of cardiovascular diseases and the cardiac pathological remodeling is the most essential part during such pathophysiological procedure. At present, there is still no specific therapy for heart failure, targeting its biological changes. Histone deacetylases (HDACs) have been proved to be involved in several regulation pathways in pathological process, one important epigenetic mechanism. Moreover, several kinds of targeted medications for specific HDACs have been developed, which provides new insights in treatment of heart failure. In this article, we will summary the functions and regulatory roles of HDACs in cardiac pathological procedure and their potential therapeutic targets.