Achieving stable metabolic control in patients with type 1 diabetes mellitus (T1DM) is highly desirable and may contribute to delaying and/or preventing the development of secondary complications. Transplantation of pancreatic islets represents a viable option for the treatment of patients with unstable T1DM with frequent severe hypoglycemia and hypoglycemia unawareness. The benefits of the transplant include improvement of glycemic control, prevention of severe hypoglycemia and amelioration of quality of life. The success of future clinical trials will depend on the implementation of an integrated therapeutic approach combining strategies to maximize islet availability and engraftment with those aiming at safely modulating the recipients' immunity to afford long-term function. The steady progress of recent years in islet cell processing and patient management after transplantation justify great optimism for the years to come.