There is no evidence of benefit from excitatory amino acid antagonists for acute stroke. Most strokes are caused by blockage of an artery with consequent loss of blood supply. Some brain tissue supplied by the artery suffers severe reduction in blood flow, and brain cells quickly die, but some tissue maintains enough blood flow to keep it alive for a period of time - probably hours in most individuals. However, the loss of blood flow sets in motion a series of events that will eventually kill the tissue. The processes that cause damage to progress involve chemical changes, one of which is the release of large amounts of glutamate (an excitatory amino acid), a substance normally used for signalling between brain cells. In large amounts, glutamate is toxic. A number of drugs have been developed to block either the release of glutamate, or the sites to which it binds on brain cells. These drugs were highly effective in animal studies. Individual clinical trials in stroke patients did not confirm benefit for any of the drugs, however. This review confirms that there are no overall benefits for these drugs in stroke, although only two of them have been tested in a large enough population to be reasonably confident that they have no major effects. Some drugs may be harmful. Over 11,000 patients have participated in trials of 13 different drugs that inhibit glutamate release or binding, but two-thirds of all data are from trials of just two drugs. For most drugs in this class, trials have been too small to provide conclusive evidence of harm or benefit. Major differences among individual drugs mean that it is impossible to conclude that all drugs with this mode of action are ineffective. Further trials remain justified, and several are ongoing.