In specific patient populations with unstable diabetes, biological beta cell replacement therapy is a valid approach to attain the desirable metabolic control. The main indications for allogeneic islet transplantation are frequent hypoglycemia and severe metabolic lability despite intensive insulin therapy, or simultaneous or sequential islet–kidney transplantation in uremic patients with type 1 diabetes. Clear outcome definitions of function and failure have been instrumental for a broader positive recognition of islet transplantation among diabetologists/endocrinologists. International collaboration has resulted in continuous improvements in cell processing techniques, patient management, and development of specific immunotherapy protocols, thus, significantly improving outcomes after islet transplantation. Excellent metabolic control, reliable prevention of hypoglycemia, and positive effects on diabetes-related complications and quality of life have been demonstrated. Islet transplantation is a safe, minimally invasive procedure that can potentially cure type 1 diabetes. Yet, limited availability of donor organs and the need for systemic immunosuppression make islet transplantation an option for only highly selected patients.