This review discusses the efficacy of clomethiazole (CMZ) in models of global and focal ischemia. The fact that neuroprotection is demonstrable by using histological, biochemical, and functional measures is emphasised. The importance of the neuroprotection observed when the drug is given after the ischemic insult and at doses that are safely tolerated by humans is discussed, with reference to requirements necessary for an experimental neuroprotective agent to be considered as a therapeutic drug for stroke. The biochemical pharmacology of CMZ is reviewed and also evaluated with reference to the possible mechanism(s) by which CMZ exerts its neuroprotective action. Finally, the clinical evidence that CMZ protects against the neurological consequences of a major stroke is outlined.