The numerous and widespread effects of adenosine provide both an opportunity for the development of novel therapeutic agents acting via adenosine receptors and the challenge of achieving selectivity of action. The feasibility of achieving selectivity is enhanced if receptor subtypes can be identified. Biochemical, functional and receptor-cloning studies are beginning to provide convergent data supporting the existence of A1, A2A, A2B and A3 receptors. However, studies of the functional significance of these receptors in intact tissues both in vitro and in vivo have lagged behind the biochemical studies. In this article, Michael Collis and Susanna Hourani review the current status of adenosine receptor classification and propose that ligands with greater selectivity need to be evaluated in a wide range of functional preparations if the therapeutic potential of this area is to be realized.