Pancreatic islet cell transplantation as a treatment for diabetes has hitherto been confined to small patient cohorts with limited success. This article summarizes the results of islet cell transplantation before and after the advent of the new ‘Edmonton protocol’of immunosuppression and management of the donor pancreas. Adopting this regimen has achieved unprecedented success and renewed interest in this potential cure for diabetes. Central to recent improvements in the technique has been the transplantation of an adequate islet mass. Improved methods to procure, isolate, and purify islets for clinical use are now being adopted as a new ‘gold standard’. The use of new immunosuppressive drugs has further improved clinical results. Corticosteroid sparing-based regimens, and agents such as humanized monoclonal antibodies, are likely to form the mainstay of immunosuppressive protocols with the aim of achieving donor-specific tolerance. Alternative sources of islet cells are also required to expand the technique in an era of reduced numbers of donor pancreata. Manipulation of stem cells and xenotransplantation may yet yield sufficient islets to overcome the problem of donor shortage. Islet cell transplantation now forms the basis of a prospective multicenter trial under the aegis of the Immune Tolerance Network. The results of this are awaited, but it appears that islet cell transplantation may yet emerge as an effective treatment option for some members of the diabetic population.