Several controlled studies with the best methodology had showed that digoxin improves the symptoms of patients with chronic heart failure and sinus rhythm, whose ventricular systolic function is impaired. The Proved and Radiance studies show that in patients receiving diuretics and digoxin, or angiotensin-converting enzyme (ACE) inhibitors, diuretics and digoxin, the withdrawal of digoxin results in clinical deterioration and worsening of exercise tolerance. In addition to an inotropic action, digitalis exerts effects in the neurocardiovascular axis, produces reduction in plasma norepinephrine, renin, aldosterone, vasopressin activity and restores a more normal sympathetic-parasympathetic autonomic balance and baroreceptor function. ACE inhibitors reduce mortality, improve symptoms and exercise tolerance in patients with chronic heart failure in class IV (Consensus I trial), in class II and III (SOLVD, treatment trial) and prevent the development of heart failure in asymptomatic patients with ejection fraction < 35% (SOLVD, prevention trial). When ACE inhibitors are administered per os, more than 3 days after acute myocardial infarction they reduce mortality, severe heart failure, re-hospitalization, and induce an unexpected reduction of recurrent myocardial infarction (SAVE trial). However, the early administration, within 2 hours after the onset of chest pain, of ACE inhibitors by intravenous infusion, does not improve survival; the hypotension may be responsible of increased mortality (Consensus II trial).