The dogma of systemic immunity can be ignored in relation to mucosal immunity. These distinct immune systems evolved based on specific environmental realities. Given the potentially hostile environment encountered by the mucosal immune system, it is a necessary adaptation that the overall tone is one of suppression. Breaches in this tone may lead to chronic inflammation. Understanding how specific components and processes of the mucosal immune system interact with the environment will elucidate the pathogenesis of IBD and lead to novel therapeutic approaches.