The complex actions of 5-hydroxytryptamine (5-HT) on blood vessels result from interactions with a multiplicity of specific 5-HT receptors. Dramatic advances recently have been made in defining the receptor subtypes involved in terms of their pharmacology and biochemistry, as well as their molecular biology, provoking an evolution of the criteria used for classifying and naming them. This article reviews the distribution and function of different 5-HT receptor types present on vascular smooth muscle, endothelium and perivascular neurones, and considers ways in which they can be positively defined and differentiated using traditional pharmacological approaches. The characteristics of each receptor type are also considered in terms of current biochemical and molecular perspectives on 5-HT receptor classification.