Type 1 diabetes is an autoimmune disease, hence the rationale for immunotherapy to halt disease progression. Based on knowledge gained from other autoimmune diseases and from transplantation, the first immunointervention trials used immunosuppressive drugs, e.g., cyclosporin, in patients with recently diagnosed type 1 diabetes. Although remarkable, the effect vanished following drug withdrawal. Efforts were then devoted to devise strategies to induce/restore self-tolerance and avoid chronic immunosuppression. Various approaches were identified from work in spontaneous models of autoimmune diabetes, including the use of β-cell autoantigens and monoclonal antibodies directed at relevant immune molecules such as costimulatory ligands, T-cell receptor molecules such as CD3, and B cells. Phase II and phase III trials were launched, results of which are now available. Although the endeavor is challenging, the experience gained indicates that immunotherapy appears as the real hope of inducing long-term remission of the disease provided the treatment is started early and that protocols are adapted based on lessons from the past.