Islet transplantation is an appealing procedure able to improve glycemic control in type 1 diabetic patients. However, the possible side effects that may be induced by immunosuppressive therapy limit its application to a select number of patients for whom the risk of immunosuppressants’ side effects can be justified. For patients with type 1 diabetes mellitus—who will take immunosuppressants regardless, as they require a solid organ transplant—islet infusion can be an interesting therapeutic option for improving metabolic compensation, whenever pancreas transplant is not possible. Hence, islet infusion can be an important therapeutic option for patients with secondary diabetes mellitus even when a minor pancreatic endocrine function remains. For these patients, results may be better than those obtained with islet infusion for patients with type 1 diabetes mellitus thanks to the lack of autoimmune reaction to the infused islets. The final result is the improvement of the glycemic compensation and most likely also an extension of the graft survival.