Several lines of evidence suggest that adenosine may be an endogenous protective agent in cerebral ischaemia. Adenosine is normally present in the extracellular fluid in most tissues of the body, including the brain, and its level increases dramatically following hypoxia or ischaemia. The rate of adenosine production is enhanced when the energy demand is larger than the rate of energy supply. Adenosine acts on specific receptors that are present in most cells in the body and that produce cellular effects that tend to antagonize a number of pathological events thought to be instrumental for ischaemic nerve cell death. Karl Rudolphi and colleagues review evidence for the neuroprotective potential of adenosine and indicate some targets for drug development.