AbstractNitric oxide (NO) is a biologically active inorganic molecule produced when the semiessential amino acid l‐arginine is converted to l‐citrulline and NO via the enzyme nitric oxide synthase (NOS). NO is known to be involved in the regulation of many physiological processes, such as control of blood flow, platelet adhesion, endocrine function, neurotransmission, neuromodulation, and inflammation, to name only a few. During neuropathological conditions, the production of NO can be either protective or toxic, dependent on the stage of the disease, the isoforms of NOS involved, and the initial pathological event. This paper reviews the properties of NO and NOS and the pathophysiology of Huntington's disease (HD). It discusses ways in which NO and NOS may interact with the protein product of HD and reviews data implicating NOS in the neuropathology of HD. This is followed by a synthesis of current information regarding how NO/NOS may contribute to HD‐related pathology and identification of areas for potential future research. J. Neurosci. Res. 64:99–107, 2001. © 2001 Wiley‐Liss, Inc.