Chronic heart failure is a complex clinical syndrome in which abnormal vascular endothelial function has been shown to occur at both the experimental and clinical levels. Alterations in endothelial function may contribute to the increased vasomotor tone and to the vascular remodeling process observed in patients with chronic heart failure. Reduced shear stress, increased activity of the various vasoconstricting neurohormonal systems, and increased levels of proinflammatory cytokines promote endothelial dysfunction in chronic heart failure. This article summarizes the major mechanisms implicated in the pathophysiology of abnormal endothelial function in chronic heart failure, as well as the novel therapeutic interventions aimed at reducing endothelial dysfunction in patients with the syndrome.