Patients with advanced chronic kidney disease exhibit an increase in cardiovascular mortality. Recent works have shown that low levels of magnesium are associated with increased cardiovascular and all-cause mortality in hemodialysis patients. Epidemiological studies suggest an influence of low levels of magnesium on the occurrence of cardiovascular disease, which is also observed in the normal population. Magnesium is involved in critical cellular events such as apoptosis and oxidative stress. It also participates in a number of enzymatic reactions. In animal models of uremia, dietary supplementation of magnesium reduces vascular calcifications and mortality; in vitro, an increase of magnesium concentration decreases osteogenic transdifferentiation of vascular smooth muscle cells. Therefore, it may be appropriate to evaluate whether magnesium replacement should be administered in an attempt to reduce vascular damage and mortality in the uremic population In the present manuscript, we will review the magnesium homeostasis, the involvement of magnesium in enzymatic reactions, apoptosis and oxidative stress and the clinical association between magnesium and cardiovascular disease in the general population and in the context of chronic kidney disease. We will also analyze the role of magnesium on kidney function. Finally, the experimental evidence of the beneficial effects of magnesium replacement in chronic kidney disease will be thoroughly described.