Vascular calcification is a prognostic marker for cardiovascular mortality in chronic kidney disease (CKD) patients. In these patients, magnesium balance is disturbed, mainly due to limited ultrafiltration of this mineral, changes in dietary intake and the use of diuretics. Observational studies in dialysis patients report that a higher blood magnesium concentration is associated with reduced risk to develop vascular calcification. Magnesium prevents osteogenic vascular smooth muscle cell transdifferentiation in in vitro and in vivo models. In addition, recent studies show that magnesium prevents calciprotein particle maturation, which may be the mechanism underlying the anti-calcification properties of magnesium. Magnesium is an essential protective factor in the calcification milieu, which helps to restore the mineral-buffering system that is overwhelmed by phosphate in CKD patients. The recognition that magnesium is a modifier of calciprotein particle maturation and mineralization of the extracellular matrix renders it a promising novel clinical tool to treat vascular calcification in CKD. Consequently, the optimal serum magnesium concentration for patients with CKD may be higher than in the general population.