Numerous experimental, epidemiological and clinical studies have pointed out a relevant role for magnesium deficiency in the development of many cardiovascular diseases. Some pharmacological treatments may interfere with magnesium turnover, and magnesium deficiency may alter the pharmacokinetics and pharmacodynamics of some cardiovascular drugs. Loop and thiazide-like diuretics increase magnesiuresis, and total bodily magnesium deficiency may appear during prolonged treatment with diuretically active doses of these drugs. The potassium retaining agents, such as amiloride, triamterene and spironolactone, tend to retain magnesium but they are not magnesium-retaining substances to the extent to which they are potassium-retaining diuretics. The interaction between magnesium and digitalis is complex. Magnesium, acting as an indirect antagonist of digoxin at the sarcolemma Na(+)-K(+)-ATPase pump, reduces cardiac arrhythmias due to digoxin poisoning. Recent controlled studies have shown that treatment with magnesium significantly reduces the frequency and complexity of ventricular arrhythmias in digoxin-treated patients with congestive heart failure without digoxin toxicity. Magnesium improves the efficacy of digoxin in slowing the ventricular response in atrial fibrillation. Digoxin reduces tubular magnesium reabsorption, and in patients with congestive heart failure this interaction may be cumulative with other causes of magnesium deficiency (diuretics, diet, poor intestinal absorption). The complex and potentially life-threatening interactions between magnesium and some cardiovascular drugs suggest that magnesium status should be carefully monitored in patients receiving such drugs. Therapy with magnesium is rapidly acting, has a safe toxic-therapeutic ratio, is easy to administer and titrate. The correction of magnesium deficit should therefore always be considered for patients with cardiopathy.