After many years of limited success in islet transplantation, researchers developing this procedure have made great strides, and several centers have now reported that islet transplantation can result in long‐term insulin independence for patients with type 1 diabetes mellitus. The improved quality of life achieved in some islet allograft recipients suggests that this important line of investigation should proceed. Yet, several factors limit the technique and these hurdles must be overcome before it can be considered a practical treatment for the millions of individuals with diabetes, be it type 1 or type 2. Most obvious is the gross disparity between the number of islets available for clinical transplantation and the number of patients with diabetes who might benefit. Other important limitations, too often lost in the discussion, include complications associated with the technique itself, the toxicity of currently available immunosuppressive drugs, and the imperfect glycemia control achieved in most patients. In fact, our ongoing analysis as to whether transplantation‐based therapy improves survival for patients with type 1 diabetes suggests that, for many at least, the opposite may be true. Two variables, as yet undefined, also need to be considered: (1) can the procedure, when done well, prevent or reverse diabetes‐associated complications and (2) what are the long‐term consequences of intrahepatic islets? Published in 2003 by John Wiley & Sons, Ltd.