Magnesium (Mg) , one of the fundamental minerals acting the co-factor of about 300 kinds of enzymes and natural Ca channel blocker, plays an important role of cardiovascular, neurological, and metabolic functions in physiological, and pathophysiological conditions. Common abnormal Mg metabolism is an absolute or relative deficiency of Mg due to an attenuated Mg intake and an enhanced urinary Mg excretion, particularly in the metabolic syndrome (MetS) , type 2 diabetes (DM) , chronic heart failure (CHF) and hemodialysis (HD) patients with diabetes. It has been reported the Mg deficiency relating to enhanced risk of MetS and type 2 DM, and to fatal cardiac events in CHF and an atherosclerotic, vascular calcification in HD patients. On the otherhand, severe and fatal hypermagnesemia is very rare, except for the condition associated with high dose administration of Mg, renal failure and an abnormally enhanced Mg absorption from damaged intestine in the mesenteric ischemia/infarction, severe constipation or ileus. In this paper, we conduct to review and discuss the pathophysiological and pathogenetical role of the abnormal Mg metabolism focused on Mg deficiency, and the protective and therapeutic significance of Mg administration in the MetS, type 2 DM, CHF and diabetic HD patients.