Adenosine is one of the body’s most vital cytoprotective molecules, mediating its effects through the adenosine family of G protein-coupled receptors. This receptor family has an essential role in physiology and pathophysiology, particularly in response to stress and injury, and therefore represents potential targets for the treatment of major global health burdens such as ischaemia-reperfusion injury, neuropathic pain and inflammation. This symposium will highlight recent advances in the mechanistic understanding and therapeutic exploitation of adenosine receptors across a variety of disease states, providing novel approaches for overcoming the preclinical-clinical bottleneck in targeting this vital receptor family.