Islet transplantation holds renewed promise as a cure for type I diabetes mellitus. Results of recent clinical trials have shown remarkable success, and have reignited universal optimism for this procedure. In spite of this success, the need for life–long immunosuppression of the recipient still limits islet transplantation to patients with poorly controlled diabetes or to those requiring kidney transplantation. It is obvious that the achievement of immunological tolerance would broaden the indication for islet transplantation to a much larger cohort of patients with type I diabetes mellitus, most likely preventing long–term complications and contributing to a much improved quality of life. Increased understanding of the basic mechanisms of tolerance induction has resulted in the implementation of numerous experimental approaches to achieve long–term survival of islet grafts in the absence of chronic immunosuppression. In this brief review we will attempt to summarize the current status of research and knowledge.