Glyceryl trinitrate (GTN) lowers blood pressure in patients with acute stroke. Nitric oxide is a key molecule involved in regulation of blood pressure and control of brain activity, both before and during stroke. As such, drugs which produce nitric oxide or control its production might be beneficial in acute stroke. Two small trials of GTN, a nitric oxide donor, have been completed, involving 127 patients with acute stroke, and show that it lowers blood pressure; however, these studies were too small to assess whether GTN is safe and effective in improving outcome and a further large trial capable of answering this question is underway. No other studies of nitric oxide donors or modulating drugs have been performed. At present, these classes of drugs should not be used in the routine management of acute stroke.