The immune system is responsible for not only eliminating threats to the body, but also for protecting the body from its own immune responses that would causeharm if left unchecked. Forkhead box protein 3 (FOXP3) is a forkhead family member with an important role in the development and function of a type of CD4+ T cell calledT regulatory cells that is fundamental for maintaining immune tolerance to self. This chapter reviews the structure ofFOXP3 and how its role in the immune systemwasdiscovered. Studies of patients with mutations in FOXP3 who suffer from a syndromeknown asIPEX (immunedysregulation, polyendocrinopathy,enteropathy,x-linked) arealsodiscussed. Investigation into howexpression of FOXP3 is regulatedand howit interactswith other proteins haverecentlyprovided considerable insightinto mechanisms bywhichthe lackof this protein couldcausedisease.Wealsodiscuss how FOXP3isinvolved in the reciprocal development ofT regulatorycells andproinflammatoryT-cells that produce IL-I? A better understandingof how FOXP3 is regulatedand the molecularbasis for its function will ultimatelycontribute to the developmentofT regulatorycell-based cellular therapiesthat could be used to restoredysregulated immune responses.