Background Gene expression differences in brain-reward regions are the key genetic mechanisms of drug addiction, yet its epigenetic mechanisms have remained unclear. Objective　To explore the epigenetic mechanisms by which chronic exogenous drugs exposure is translated into drug addiction. Content　Evidence pertaining to DNA methylation and histone epigenetic regulation and microRNA in drug dependence or addiction is reviewed. Trend　 These novel insights of epigenetic variations mediating drug abuse and dependence might pave new pathes for improving treatments of drug addiction.