Whole organ pancreas and pancreatic islet transplantation are currently the only forms of clinically available β-cell replacement. Both therapeutic options can provide good glycemic control and prevention or stabilization of diabetic complications, but at the price of permanent immunosuppression. Therefore, the indication for transplantation of type 1 diabetes patients must be balanced carefully and should be restricted to a subgroup of patients with extreme lability of metabolic control and frequent hypoglycemia despite optimal medical therapy.