New hope for the treatment of type 1 diabetes has recently emerged from the encouraging results of islet cell transplantation in humans during the last few years. Although still facing considerable problems, the challenge to achieving insulin independence has been overcome in some patients who received an islet graft. However, the success of clinical trials is still limited by the inability to transplant enough viable human islets to compensate for the insulin-deficient state, the number of islets that engraft following transplantation, the rejection process, and the recurrence of autoimmunity. The important advances in immunosuppressive regimens, organ procurement techniques, isolation techniques, and availability of defined collagenase blends have contributed to the continuing promise of making islet cell transplantation the treatment of choice for type 1 diabetes mellitus.