The free-radical gas nitric oxide (NO) plays an important role in a diverse range of physiological processes. It is synthesised from the precursor L-arginine by the enzyme NO synthase (NOS), which transforms L-arginine into NO and L-citrulline. This synthetic pathway exists in the central nervous system (CNS), and NO appears to be a messenger molecule in the CNS, fulfilling most of the criteria of a neurotransmitter. Recent studies indicate that NO may play an important role in ethanol dependence. The purpose of this review is to address the role of NO in ethanol dependence. Inhibitors of NOS modulate withdrawal from ethanol, diminishing many signs of withdrawal. These data suggest that NO may be involved in the expression of withdrawal signs, and they leave open the possibility that NO may mediate the development of many of these signs. Preliminary data to date suggest that glutamate neuro-transmission may be related to these beneficial effects of NOS inhibitors on signs of withdrawal. Emerging data further suggest that NO may have a general role in development of ethanol dependence. Thus, modulation of NO systems may be a potential therapeutic target for treatment of ethanol abuse and dependence.