Ischaemic stroke causes loss of brain function in millions of people worldwide each year. Despite the enormity of the problem, no currently approved therapy reduces stroke size or neurological disability. This contrasts with a number of recently developed agents, reviewed here by Walter Koroshetz and Michael Moskowitz, which limit infarct size in animal stroke models. Therapies that dissolve clot and restore blood flow, block excitatory neurotransmission, prevent the ischaemic inflammatory response or scavange free radicals have the potential to revolutionize stroke treatment if proven beneficial in ongoing, placebo-controlled clinical trials. Developments in the experimental arena continue to reinforce the need to characterize the pathophysiological stages leading to brain infarction and recovery.