Many different pathways contribute to the maintenance of tolerance to harmless antigens in the intestine. When these important pathways are compromised, chronic intestinal inflammation can develop. In particular, naturally occurring CD4+CD25+ regulatory T cells have been shown to play an important role in the prevention and cure of colitis in animal models of intestinal inflammation. These regulatory T cell responses may be influenced by the local environment in the intestine. For example, functionally specialised populations of dendritic cells exist in the intestine which may favour regulatory type responses. Understanding how these pathways intersect may lead to the development of more specific therapies for the treatment of inflammatory bowel disease.