Nitrates are widely used in the therapy of heart failure despite the absence of US Food and Drug Administration approval or of a marketing effort by pharmaceutical companies. Their efficacy is related to the generation of nitric oxide, a vasodilator and antiproliferative substance that may be deficient in cardiovascular disease states. The hemodynamic action of nitrates reduces impedance to left ventricular ejection, increases capacitance of the venous system to reduce cardiac filling pressure and results in increased exercise capacity. The antiproliferative effect induces regression of left ventricular remodeling. Co-administration of hydralazine inhibits the development of nitrate tolerance. Long-term administration of combined therapy causes regression of structural remodeling and reduced mortality from heart failure. The short-term and long-term efficacy of this combination added to conventional therapy should be tested in large-scale trials.