Long-term culture of human islets provides opportunity for improving results of islet transplantation. The techniques of long-term culture are reproducible and can result in improved function of the islet after transplantation into NOD-SCID mice. We have been able to cure streptozotocin-induced diabetes by islets cultured for more than 6 mo. Culture conditions play an important role in the success of the procedure. Culture success is dependent on the media type, additives, type of colloid or protein used, purity of the islets, and concentration and volume of the tissue. Cellular and structural changes occur over time in culture. These changes may explain the improved efficacy of the islet graft after short and intermediate culture periods. Further research into long-term culture of islets is necessary to fully explore the potential of the technique.