The author comments on the DPT-1 Trial and why the observed negative outcome in preventing diabetes in first-degree relatives of type 1 diabetic patients by parenteral insulin administration may have occurred and what can be gathered from this large study. There were three main lessons to be learned from the DPT-1 Trial as follows. (1) Large preventive trials of type 1 diabetes are feasible in first-degree relatives of type 1 diabetic patients and other preventive approaches may be now envisaged. (2) The natural history of type 1 diabetes, at least in its final years before clinical onset, has been elucidated and reiterates the relevance of our present predictive tools (autoantibodies) for identifying individuals at risk for the disease. (3) Strict follow-up of enrolled subjects in trials permits an earlier diagnosis of the disease with less frequency of ketoacidosis and implementation of insulin therapy when higher C-peptide levels are present. DPT-1 has paved the way on how to proceed and new trials will be planned benefiting from such experience.