This article focuses on the key concept that a basal production of nitric oxide (NO) is required as a background for biological modulation, although an excess can be cytotoxic. Studies of ischaemia and neurodegeneration have tended to emphasise detrimental effects of excess NO, but this review contrasts the emerging importance of diminished NO or interference with its action in vasospasm following subarachnoid haemorrhage (SAH) in ageing and in atherosclerosis. Clinical intervention in cerebral ischaemia will require specificity of action, since NO appears to be protective or detrimental depending on the time, source, and distribution of its production. It may be possible to utilise targeted action on the different forms of NO synthase or the specific redox forms of NO in different tissue areas.