Recently, a central role for the A2b adenosine receptor in a variety of cardiovascular functions including inflammation, erectile function, coronary artery dilation, asthma and cardioprotection has been demonstrated. Despite this evidence, the low-affinity A2b adenosine receptor is still poorly understood. This receptor appears to be very promiscuous in its coupling. In most tissues, it couples to Gs much like its cousin, the A2a adenosine receptor, but in mast cells and now, most recently, in cardiac fibroblasts, the A2b receptor also couples to Gq. Because of its low affinity, this receptor was originally thought unlikely to play any important physiological role. But the sensitivity of A2b adenosine receptors can be greatly increased by interaction with protein kinase C (PKC) making this receptor, under various conditions, both an activator and a target of PKC. We have recently documented a third coupling involving Gi. This plasticity and versatility of A2b adenosine receptors position them as potential triggers of signalling in multiple signalling cascades in many physiological responses, making this a most interesting receptor indeed.