Autoimmune conditions caused by injurious immune responses against self-antigens can be ameliorated if the inappropriate responses to self-components that cause tissue injury can be modulated by regulatory cells or shut off via the induction of anergy or via deletion of pathogenic immune responses. Antigen encounter at the gut mucosa can lead to suppression of injurious immune responses to self-antigen via these mechanisms. This type of immunological event is termed oral tolerance. In this review, we examine the mechanisms behind the induction of oral tolerance and provide findings from its use as a form of treatment for autoimmune diseases.