Cytokines, particularly the proinflammatory cytokines, whose role and natural regulation in inflammatory bowel disease are reviewed here, are produced by many cell types, including immune cells. Cytokines function as important hormones of the immune system, and many act both regionally and systemically via specific receptors. The demonstration of increased circulating and mucosal levels of proinflammatory (and other) cytokines (and receptors) in active inflammatory bowel disease does not by itself constitute any proof as to the primary involvement of these mediators. However, they may contribute significantly to disease manifestations, and specific therapeutic intervention at the cytokine or cytokine receptor level may show up to be clinically most relevant. This is underscored by the increasing evidence that proven therapies of inflammatory bowel disease to a great extent seem to function through cytokine modulation.