The discovery of endothelial regulatory properties in the modulation of the vascular response to pharmacological agents and its fundamental role in the phenomenon of flow-dependence has enabled the demonstration of the mode of action of coronary vasodilators on the large epicardial vessels where most coronary spasm occurs. Nitrate derivatives are remarkably selective in their effects on the large vessels which dilate in an endothelial-independent manner, which makes them very effective in the prevention and treatment of coronary spasm occurring, for example, during angioplasty. On the other hand, arterial vasodilators, like calcium antagonists or potassium agonists have decreased vasodilatory effects on these conductance vessels in the presence of endothelial lesions as their action is partially or entirely endothelium-dependent. By their additive coronary vasodilator effects, the association of these two groups of vasodilators provides greater therapeutic efficacy in the prevention of angina whatever its cause.