Diabetes mellitus is one of the chronic noncommunicable diseases that have increased markedly in this century. The discovery of insulin and other drugs for lowering hyperglycemia have certainly reduced mortality from acute complications of diabetes and improved the quality of life of many diabetic patients. Recent advances in research into the etiology and natural history of diabetes have increased our knowledge about different types of diabetes to such an extent that primary prevention of diabetes mellitus is becoming a reality. Until now, few studies have attempted to test measures for primary prevention of diabetes. Therefore, the data supporting the possibility for primary prevention are largely indirect and need to be tested in preventive trials or in community-based prevention programs. We believe, however, that the time is right to start action in populations in which the prevalence of diabetes is known to have clearly increased recently. We summarize the evidence that can be used as the scientific basis of primary prevention of diabetes mellitus.