Type 1 diabetes (T1D) is a chronic autoimmune disorder resulting from immune-mediated destruction of insulin-producing beta cells within the pancreatic islets. Prediction of T1D is now possible, as having 2 or more islet autoantibodies confers a 100% risk of diabetes development. With the ability to predict disease development, clinical trials to prevent diabetes onset have been completed and are currently under way. This review focuses on the natural history, prediction, and prevention trials in T1D. We review the lessons learned from these attempts at preventing a chronic autoimmune disease and apply the paradigm from T1D prevention to other autoimmune disorders.