Recent epidemiologic and clinical evidence emphasizes the association of hypertension, peripheral insulin resistance, hyperinsulinemia, and/or frank diabetes mellitus. The underlying basis for this clinical association remains unknown, and much attention has been focused on a possible role for hyperinsulinemia in these processes. However, evidence also suggests direct hypotensive effects of insulin. It is therefore unclear to what extent hyperinsulinemia contributes to, rather than merely reflects, these multiple metabolic abnormalities. Recent research links both hypertension and diabetes to common defects in calcium and magnesium metabolism, at least in part described by increased cytosolic free calcium, suppressed intracellular free magnesium, and their associated intracellular and hormonal alterations. Thus, hypertension, peripheral insulin resistance, and hyperinsulinemia may be different clinical manifestations of a common underlying cellular defect in divalent ion metabolism.