Major advances have been made in our understanding of the molecular structure and function of the alpha-adrenoceptors. Many new subtypes of the alpha-adrenoceptor have been identified recently through biochemical and pharmacological techniques and several of these receptors have been cloned and expressed in a variety of vector systems. Currently, at least seven subtypes of the alpha-adrenoceptor have been identified and the molecular structure and biochemical functions of these subtypes are beginning to be understood. The alpha-adrenoceptors belong to the super family of receptors that are coupled to guanine nucleotide regulatory proteins (G-proteins). A variety of G-proteins are involved in the coupling of the various alpha-adrenoceptor subtypes to intracellular second messenger systems, which ultimately produce the end-organ response. The mechanisms by which the alpha-adrenoceptor subtypes recognize different G-proteins, as well as the molecular interactions between receptors and G-proteins, are the topics of current research. Furthermore, the physiological and pathophysiological role that alpha-adrenoceptors play in homeostasis and in a variety of disease states is also being elucidated. These major advances made in alpha-adrenoceptor classification, molecular structure, physiologic function, second messenger systems and therapeutic relevance are the subject of this review.