The induction of antigen (Ag)-specific tolerance is critical for the prevention of autoimmunity and maintenance of immune homeostasis. Recently, attention has been focused on induction of active suppression by regulatory T cells (Treg cells). Also, a role for dendritic cells (DCs) in the promotion of peripheral tolerance has been demonstrated by several studies and is the subject of intensive investigation. It is currently believed that the maturation/activation state of DCs might be a control point for the induction of peripheral tolerance through modifications of the activation state of T cells. Several lines of experimental evidence suggest that unique DC subsets or discrete functional states of the DCs might be devoted to the promotion of Treg cell differentiation. The present review summarizes the emerging literature on the developmental origin and function of human Treg cells and tolerogenic/regulatory DCs. Furthermore, clinical implications of these studies for cellular therapy of immune-mediated pathologies are discussed.