Human urotensin II (U-II) is a cyclic peptide generated by proteolytic cleavage from a precursor prohormone. It was first isolated from the fish spinal cord and has been recognized as a hormone in the neurosecretory system of teleost fish. It is expressed in the human central nervous system as well as other tissues, such as kidney, spleen, small intestine, thymus, prostate, pituitary and adrenal gland and circulates in human plasma. The plasma U-II level is elevated in renal failure, congestive heart failure, diabetes mellitus, systemic hypertension and portal hypertension caused by liver cirrhosis. The effect of U-II on the vascular system is variable, depending on species, vascular bed and caliber of the vessel. The net effect on vascular tone is a balance between endothelium-independent vasoconstriction and endothelium-dependent vasodilatation. Urotensin II is also a neuropeptide and may play a role in tumor development. The development of U-II receptor antagonists may provide a useful research tool as well as a novel treatment not only for cardiovascular diseases.