Oral tolerance is the immunologic mechanism by which the mucosal immune system maintains unresponsiveness to the myriad of antigens in the mucosal environment which might otherwise induce untoward immune responses. Recent studies have shown that it is mediated by several distinct, yet interacting mechanisms including the generation of suppressive T cells producing antigen nonspecific cytokines and the induction of clonal deletion and/or anergy. In this review of oral tolerance, we discuss these mechanisms in detail and show how oral tolerance or lack thereof may explain the occurrence of mucosal inflammation. In addition, we discuss how induction of oral tolerance can be used to treat autoimmune states.