Although there is a continual improvement in the understanding of the pathophysiology of brain ischaemia and reperfusion, the pharmacological approach of treating or preventing brain ischaemic injury has had limited clinical impact so far. The great majority of clinical trials testing neuroprotectants for the treatment of acute ischaemic stroke have failed to demonstrate any benefit on any major outcome endpoint. Several strategies combining physiologic (oxygen, hypothermia), pharmacologic (erythopoietin derivatives) and thrombolytic therapies may, however, be promising in future, provided a more rigorous design of the clinical trials is achieved. The place of anaesthetics as clinical effective neuroprotectants in the perioperative period remains to be established.