Autoimmune diseases are characterized by the loss of tolerance toward self-antigens and the induction of destructive immune responses leading to tissue damage. Most patients with autoimmune diseases are treated with immunosuppressive drugs that suppress the immune response in a non-specific fashion, which is inevitably accompanied by several side effects. Antigen-specific immunomodulation and patient-tailored therapies are likely to solve these issues and to elicit long-term protection against disease flares. This Viewpoint analyzes the potential use of DC for induction of antigen-specific tolerance in autoimmune disease settings.