More than 471 patients with type 1 diabetes have received islet transplants at 43 institutions worldwide in the past 5 years. High rates of insulin independence have been observed at 1 year in the leading islet transplant centers, and an international multicenter trial has demonstrated reproducible success of the approach. Loss of insulin independence by 5 years in the majority of recipients remains of concern, and immunosuppressant drug side effects necessitate stringent inclusion criteria for islet-alone candidates that have the most severe, unstable glycemic control despite optimal insulin therapy. The advent of new immunosuppressive drugs with superior side-effect profiles (eg, LEA29Y and FTY720) may open up opportunities for more “islet-friendly” approaches. Future opportunities to expand the donor pool using living donor islet transplantation are within reach, and will be enhanced considerably with both donor and recipient adjunctive treatment using islet-specific growth-factors.