The primary prevention of type 2 diabetes mellitus (T2DM) is of great importance. There is now substantial evidence that T2DM can be prevented or delayed by lifestyle modification. A statistically significant reduction of relative risk of newly diagnosed T2DM was observed in large clinical trials with metformin, acarbose or orlistat in subjects with impaired glucose tolerance as well as with troglitazone in women with previous gestational diabetes. A relative risk reduction of newly diagnosed diabetes was observed in prospective, double blind clinical studies evaluating the effect of different antihypertensive drugs (ACE-inhibitors, angiotensin repector blockers, calcium channel blockers) or that of lipid-lowering agents (pravastatin) on the cardiovascular morbidity and mortality in high risk patients. In studies with postmenopausal hormone replacement therapy a relative risk reduction of newly developed T2DM was also observed. Thus, T2DM should be considered as a preventable disease. Nevertheless, it is noteworthy that oral antidiabetic drugs with an indication of preventing T2DM are not registered in several countries at present, so that drug therapy should not be used as a routine for preventing diabetes. On the other hand, patients with pre-diabetes (impaired fasting glycaemia, impaired glucose tolerance) should be given counseling on weight loss as well as instruction for increasing physical activity in order to prevent T2DM.