Vascular calcification is a common clinical complication in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. It is a significant risk factor for future cardiovascular events in these patients. There are currently no effective medications to slow or reverse the progression of vascular calcification. It has been previously reported that vascular calcification is an actively cellular-mediated pathological process, which shares many similarities to that of bone formation and bone metabolisms. The osteogenic transition of vascular smooth muscle cells plays an important role in vascular calcification. Recently, epigenetic regulators have emerged as key mediators of vascular calcification. This review summarizes our current understanding of epigenetic regulators such as DNA methylation, histone modification and non-coding RNAs in the pathogenesis of vascular calcification. Targeting epigenetic regulators may represent a novel strategy to treat vascular calcification.