Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology that results in progressive joint destruction and ultimately to disability. Currently effective biologic therapies, exist for approximately 40% of patients, but disease activity remains inadequately controlled in others. Therefore, it is crucial to identify specific markers that predict therapeutic response in various patients, prior to the initiation of therapy. DNA methylation , as a epigenetic factor, is increasingly being explored as a potential theranostic biomarker. It has been suggested that DNA methylation might contribute to RA development, nonetheless , with conflicting results. Epigenetic modules have provided a possible interface through which genetic and environmental risk factors contribute to the susceptibility and pathogenesis of RA. Hence, epigenetic regulators may provide promising drug targets to develop novel therapeutic drugs for tailored treatment of RA patients. Here we review the current knowledge regarding the role of DNA methylation in RA and indicate its potential therapeutic implications.