SummaryThe freely diffusible gaseous compound nitric oxide (NO) has been shown to be an important messenger in many organ systems throughout the body, and particularly in the central nervous system (CNS). The importance of NO as an intermediary in cell communication in the brain is highlighted by the fact that the excitatory amino acid glutamate, the most abundant CNS neurotransmitter, is an initiator of the reaction that forms NO. Because of its numerous physiological and pathophysiological roles, the impact of NO on clinical medicine is developing. NO can act as a "double-edged sword" and it has been demonstrated that clarification of the dual effect of NO might have implications for clinical medicine, and could lead to the emergence of therapeutic opportunities. Accordingly, NO was proclaimed "Mole cule of the Year" in 1992 by the journal Science, while discovery of the pathways and roles of NO was acknowledged with the Nobel Prize in 1998. Additionally, the ubiquity of NO in the CNS implies that drugs designed to modify the biological activity of NO may have distinct effects. Thus, further clinical applications of NO, of its analogs or of newly developed NOS inhibitors are forthcoming. The therapeutic challenge would be to succeed in manipulating the NO pathways selectively.