For decades, the inability of insulin therapy to physiologically control glycemia in type I diabetic patients has motivated the search for insulin-delivering grafts. Islet autotransplantation is such a therapeutic approach to prevent diabetes mellitus following a major pancreatectomy, whereas allotransplantation is generally prescribed for type I diabetic patients with a functional solid organ graft, or for patients awaiting one. As of today, over 150 patients have been autotransplanted world-wide, following total or subtotal pancreatectomy, permitting an insulin-independence in nearly 40% of patients. Furthermore, more than 350 islet allotransplantations have been performed. Recent results show improved metabolic control in over 50% of cases and insulin-independence in approximately 20%. This chapter presents a literature review including preliminary human islet transplantation data from the University of Geneva.