The development of heart failure is accompanied by the activation of neuroendocrine compensatory mechanisms (see chapter “Endocrine response to heart failure”). Although these responses are initially aimed at preserving cardiovascular homeostasis, they eventually lead to a further deterioration of myocardial performance due to excessive vasoconstriction and volume overloading. The treatment of severe heart failure has therefore three objectives: to increase myocardial contractility, to decrease venous return (preload) and to lower peripheral resistance (afterload). The last two objectives are the target of the therapy with vasodilators.