Risk of progression to IDDM has been assessed extensively in first-degree relatives of IDDM patients, and highly specific prediction is possible within a small subset of this population. Because approximately 90% of future cases will come from those who have no close relative with IDDM, prediction and intervention within the general population will become the main priority for the future. This review presents a decision tree analysis of risk of progression to IDDM, highlights the different prognosis of markers when applied to those with and without a family history of the disease, and proposes a strategy for disease prediction in the latter. Large collaborative studies in well-characterized populations will allow new predictive markers and models to be evaluated, and strategies of intervention to be tested with maximum efficiency and minimal delay.