Type 1 diabetes in humans is a serious autoimmune disorder of children that is still poorly understood, unpreventable, and irreversible. Study of its animal models, notably the NOD mouse and BB rat, has generated a wealth of information concerning genetics and immunopathogenesis, but that information has still not altered the way in which we treat children with diabetes. In this review we attempt to identify the most promising avenues of continuing research in these models and the most important issues that must be faced by the designers of human therapies based on the animal dataset.