The incidence of type 1 diabetes continues to increase worldwide. Despite major strides in the daily care of patients with the disease, the patients' contribution to overall morbidity and mortality statistics and health care economic burden to society is disproportionately large because of the high rate of microvascular and macrovascular complications. The quest for prevention of type 1 diabetes has been made feasible by the unraveling of the immunogenetics of the disease and the identification of at-risk subjects by an enhanced understanding of the natural history of the prediabetic period. A combination of immunologic, metabolic, and genetic markers can be used to accurately predict the disease in higher-risk relatives and the general population. This has enabled initiation of worldwide trials (Diabetes Prevention Trial-Type 1, European Nicotinamide Diabetes Intervention Trial, and Trial to Prevent Diabetes in Genetically at Risk) aimed at the prevention of the disease. Various promising agents are being considered for use in different at-risk populations in the near future.