Nitric oxide (NO) is an important biological mediator with effects on homeostasis, neurotransmission and immune function. Chronic inflammation of the intestinal mucosa in patients in ulcerative colitis and Crohn's disease has been reported to be associated with enhanced production of NO and nitric oxide synthase (NOS) activity. Whereas small amounts of NO produced by endothelial constitutive calcium-dependent NOS may act to preserve intestinal mucosa integrity, large amounts of NO synthesised by inducible calcium-independent NOS may play a key role in further aggravation of the inflammation and may be associated with the development of intestinal mucosal injury and amplification of immune response in patients with inflammatory bowel disease (IBD). In this article we review NO pathways, mechanisms of action, functions, regulation, immunogenetics and the role played in IBD. A deeper knowledge of the NO physiopathology may allow new therapeutical approaches in IBD patients. In fact, the development of selective inhibitors of NOS isoforms could provide a novel therapeutic option in the management of IBD patients.