The vascular Na+ pump maintains intracellular ionic concentration and controls membrane potential. Its inhibition by cardiac glycosides enhances the intracellular Na+ concentration. This in turn activates the Na+-Ca2+ exchange mechanism, which induces intracellular Ca2+ increase, membrane depolarization, and noradrenaline release from perivascular adrenergic nerve endings; mechanisms that promote vasoconstriction. This article reviews the relevance of the Na+ pump in vascular tone regulation and the modulation of its activity by the endothelium. The endothelium negatively modulates the vasoconstriction elicited by Na+ pump inhibition by the release of nitric oxide, according to some authors, or an unknown factor, as suggested by others. The possible existence of endogenous digitalis-like factors is also reviewed, as is the involvement of the vascular Na+ pump in some cardiovascular disorders and aging.