Although thrombolytic therapy has represented an advance in the treatment of acute ischaemic stroke, therapy overall has remained suboptimal, as many patients present too late to benefit and others fail to obtain substantial benefit from thrombolysis. As a result, clinical research in stroke therapy has focused increasingly on alternative strategies to minimise neurological damage, especially in patients who do not receive thrombolytic therapy. However, optimism for neuroprotection has taken a tumble recently,*and has now suffered once again - results from clinical trials of 3 different putative neuroprotectants presented at the American Stroke Association 25th International Stroke Conference [New Orleans, US; February 2000] failed to show a beneficial effect on primary stroke outcome measures. Citicoline, lubeluzole and the glycine antagonist gavestinel all failed to better results achieved with placebo, although results from an imaging substudy suggested a benefit of citicoline on infarct volume in selected patients.