5-Hydroxytryptamine (5-HT) is involved in regulation of both physiological and pathophysiological conditions in tissues throughout the body. 5-HT induces vascular smooth muscle constriction in most vessels. The vasoconstrictive effects of 5-HT are mediated by 5-HT_1B and 5-HT_2A receptors located on the membrane of smooth muscle cells, except in the intracranial arteries which constrict only through 5-HT_1B receptors. 5-HT also acts as vasodilator because it releases nitric oxide from endothelial cells. This response is dominantly mediated by 5-HT_1B receptors but not by 5-HT_2A receptors. In this review, we focus on the action of 5-HT via G protein-coupled 5-HT receptors involved in some vascular-related pathophysiological responses. Furthermore, we describe the possibilities of 5-HT receptors as targets for drug therapy against saphenous vein grafts diseases (especially in patients with diabetes mellitus), migraine and pulmonary arterial hypertension.