BACKGROUND: Despite the prognostic significance of mineral and bone disorders in patients undergoing hemodialysis, very few studies have focused on magnesium metabolism in this population. Nephrologists have paid much attention to hypermagnesemia, which is sometimes caused by magnesium administration, but the clinical implication of low magnesium has been largely overlooked. Recently, several cohort studies have reported that lower serum magnesium levels are associated with an increased risk of all-cause and cardiovascular mortality among hemodialysis patients. In addition to its beneficial effect on endothelium, magnesium has been shown to inhibit the progression of vascular calcification both in vitro and in vivo. Although the exact underlying mechanism is still uncertain, magnesium can suppress the maturation of calciprotein particles, a candidate culprit for vascular calcification, which is promoted by high phosphate. Thus, magnesium seems to be useful to alleviate the phosphate-induced calcification stress. Consistently, the risk of cardiovascular death associated with hyperphosphatemia is attenuated among hemodialysis patients with high serum magnesium levels, whereas this risk is exacerbated among those with low serum magnesium levels. In the context of the bone-vascular axis, magnesium may also be involved in the risk of fracture. It should be noted that, although total serum magnesium levels of hemodialysis patients are often above the reference range, the concentration of ionized magnesium, a biologically active form of magnesium, is largely normal or even low. SUMMARY: A growing number of observational studies have uncovered the relationship between lower serum magnesium levels and poorer survival of hemodialysis patients. Magnesium modulates the pathogenesis of mineral and bone disorders and might provide a novel therapeutic approach for vascular calcification. Key Messages: Future intervention studies should clarify whether magnesium supplementation and/or increasing dialysate magnesium concentration improves the prognosis of hemodialysis patients.