A host of physiological processes associated with the cardiovascular (CV) system, central nervous system (CNS), and a variety of other organ systems and tissues are regulated by agents, primarily adenosine (ado) and adenosine triphosphate (ATP), that act via cell-surface purine receptors. These receptors have therefore been the focus of a variety of programmes directed at the discovery and development of new therapeutic agents, most notably for the treatment of disorders of the CV system. Currently, only a handful of agents, including ado, theophylline, dipyridamole, and ticlopidine, are approved for clinical use. A variety of new agents intended for use in CV disease, disorders of the CNS, such as Parkinson's disease, treatment of pain, inflammatory disorders, and diverse other pathophysiological conditions are in clinical development. Historically, ado receptors have been the primary target. Recent research efforts have begun to examine alternative strategies including agents that modulate endogenous levels of extracellular ado and agents that act via P(2) receptors.