Vasoprotective drugs decrease the vulnerability of blood vessels to cardiovascular risk factors such as hypertension and hypercholesterolemia. Mechanistic treatment end-points of hypertension (normalization of endovascular pressure) may not correct non hypertensive components of the pathobiology of hypertension. Estrogen replacement therapy, antihypertensive treatment with angiotensin-converting enzyme inhibitors, and manipulations of nitric oxide metabolism may have beneficial effects on vessels in the absence of blood pressure normalization. Estrogens and L-arginine, the precursor of nitric oxide, can partly correct impaired endothelium-dependent vasodilation, a pathophysiologic hallmark of hypertensive states. Angiotensin-converting enzyme inhibitors preserve endothelium-dependent vasodilation and protect arteries against the atherogenic effects of hypercholesterolemia by a non-hypolipidemic, non-hypotensive mechanism.