Endothelin-1 (ET-1) was first characterized as a potent vasoconstrictor and is overexpressed in the vasculature in different models of hypertension, such as deoxycorticosterone acetate-salt rats, Dahl salt-sensitive rats, and stroke-prone spontaneously hypertensive rats. Moreover, patients with moderate to severe hypertension present increased vascular levels of prepro-ET-1 mRNA. In addition to their blood pressure-lowering effects, ET receptor antagonists are able to reduce vascular growth. Recent data suggest the involvement of an inflammatory response in the effects of ET-1, which contributes to vascular remodeling and endothelial dysfunction. Increasing evidence underscores the potential therapeutic benefit of ET receptor antagonists in different hypertension-related complications, not only in essential hypertension, but also in patients with type 2 diabetes.