Multiple sclerosis (MS) is a classic neuroimmunologic and neurodegenerative disease. A growing body of evidence suggests that epigenetic changes are associated with the development of MS. Epigenetic modifications can influence the expression of genes, but will not change the sequence of DNA. DNA methylation, histone modification and microRNA-associated post-transcriptional gene silencing are three key epigenetic mechanisms that influence gene expression. Epigenetic mechanisms may regulate MS onset by affecting the genetic susceptibility and environmental risk factors, and by influencing the inflammatory demyelination and neurodegeneration involved in MS pathology. In this review we summarized recent studies on the role of epigenetic changes in the pathophysiology and treatment of MS.