Nitric oxide (NO) is a messenger that is involved in many physiological events including host defence, vascular tone and neurotransmission. It plays a role in many nervous system functions including synaptogenesis during brain development, synaptic plasticity associated with learning and memory, and regulation of cerebral blood flow. NO is produced from at least 3 different NO synthase (NOS) isoforms: neuronal NOS (type-1; nNOS), immunological NOS (type-2; iNOS) and endothelial NOS (type-3; eNOS).Under conditions of excessive formation. NO may elicit neuropathological changes. For example, excess NO from nNOS has been implicated in neuronal damage associated with stroke, excitotoxins, mitochondrial toxins and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Activation of iNOS may play a role in the pathogenesis of multiple sclerosis and severe AIDS dementia, while derangements in NO formation from eNOS may play a role in the pathogenesis of migraine headaches. Thus, the development of specific NO inhibitors has become a major challenge. Selective inhibitors are beginning to be developed for the various isoforms of NOS, which raises the possibility that medicinal chemists will be able to develop well tolerated and selective NOS inhibitors that may be used for the treatment of CNS disorders that are due to derangements of NO.