Pancreatic islet cell transplantation is an attractive treatment of type 1 diabetes (T1D). The success enhanced by the Edmonton protocol has fostered phenomenal progress in the field of clinical islet transplantation in the past 5 years, with 1-year rates of insulin independence after transplantation near 80%. Long-term function of the transplanted islets, however, even under the Edmonton protocol, seems difficult to accomplish, with only 10% of patients maintaining insulin independence 5 years after transplantation. These results differ from the higher metabolic performance achieved by whole pancreas allotransplantation, and autologous islet cell transplantation, and form the basis for a limited applicability of islet allografts to selected adult patients. Candidate problems in islet allotransplantation deal with alloimmunity, autoimmunity, and the need for larger islet cell masses. Employment of animal islets and stem cells, as alternative sources of insulin production, will be considered to face the problem of human tissue shortage. Emerging evidence of the ability to reestablish endogenous insulin production in the pancreas even after the diabetic damage occurs envisions the exogenous supplementation of islets to patients also as a temporary therapeutic aid, useful to buy time toward a possible self-healing process of the pancreatic islets. All together, islet cell transplantation is moving forward.