Deficits in immunological tolerance against self-antigens and antigens provided by the diet and commensal microbiota can result in the development of inflammatory and autoimmune disorders. Dendritic cells (DCs) are pivotal regulators of the immune response, specialized in antigen presentation to drive T cell priming and differentiation. DCs also have a tolerogenic function, participating in the enforcement of central and peripheral tolerance and the resolution of ongoing immune responses. Thus, DCs control effector and regulatory mechanisms relevant to the pathology of autoimmune disorders. In this review, we discuss recent findings regarding the control of the adaptive immune response by tolerogenic DCs. A thorough understanding of the mechanisms that control the tolerogenic DC phenotype will guide the development of novel strategies for the treatment of autoimmunity.