The therapeutic modulation of the nitric oxide (NO) system has generated considerable interest as a new way for managing many disease processes. In stroke, a useful strategy is to increase NO availability and thereby exploit its beneficial antiplatelet, antiatherosclerotic, haemodynamic and neuroprotective properties. Pharmacologically, this can be achieved by providing NO substrate, using NO donors or by upregulating nitric oxide synthase. Alternatively, one can reduce NO availability by inhibiting NO synthase and thereby limiting its pro-inflammatory and neurotoxic properties. This article reviews developments in NO-related therapeutics for treatment of stroke, with a particular emphasis on compounds that are in the clinical research and development pipeline. Although the routine use of NO therapeutics for the prevention or treatment of stroke cannot currently be recommended, we are evidently at an exciting stage in their pharmacological development. Definitive randomised controlled trials in stroke patients are required as a matter of urgency.