Accelerated developments and improved understanding of the issues that face clinical islet cell transplantation during the last 20 years have led this simple concept to a successful treatment for diabetes. Islet cell transplantation involves the extraction of islets of Langerhans from organ donors through complex digestion and purification processes. After implantation in patients with type-1 diabetes, the treatment can provide near perfect, moment-to-moment control of blood glucose, far more effectively than injected insulin. The procedure offers the benefits of whole pancreas transplantation, but with less risk. Since the introduction of “Edmonton Protocol”, significant advances in islet isolation techniques and purification technology, novel immunosuppressants and tolerance strategies have renewed interest in clinical islet transplantation for the treatment of diabetes mellitus. The “Edmonton Protocol” has been successfully replicated by other centers in an international multicenter trial. A number of key refinements in pancreas transportation, islet preparation and newer immunological conditioning and induction therapies have led to continued advancement through extensive collaboration between key centers. This article provides an overview of the history of islet transplantation followed by discussion on current controversies of donor selection, pancreas procurement, hypothermic preservation solutions, current islet isolation technique, islet transplantation procedure, post transplantation immunology, and developments for future.