Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptor have been cloned: A1, A2A, A2B and A3. Significant advancement has been made in our understanding of the molecular pharmacology and physiological relevance of adenosine receptors but our knowledge of A2B receptors lags behind that of other receptor types. Only recently have potentially important functions been discovered for the A2B receptors, prompting a renewed interest in this receptor type. A2B receptors have been implicated in the regulation of vascular smooth muscle tone, cell growth, intestinal function and neurosecretion. In this review, Igor Feoktistov, Riccardo Polosa, Stephen Holgate and Italo Biaggioni focus on the role of A2B receptors in mast cell activation and the potential relevance of this action on asthma.