The prevention of insulin-dependent diabetes (IDD) in humans remains an elusive goal, despite the broad spectrum of therapeutic interventions that prevent the development of IDD in the non-obese diabetic (NOD) mouse. Can an animal model in which spontaneous autoimmune pathology is interrupted so easily serve as an archetype for the design of clinical trials aimed at the prevention of IDD in humans? In this article, Mark Bowman, Edward Leiter and Mark Atkinson review the intervention strategies that prevent IDD in the NOD mouse and indicate why these studies may well be relevant to the prevention of IDD in humans.