Despite some controversies, especially in 2008, evidence is mounting by a number of randomised controlled trials in recent years that blood-glucose-lowering therapy (as an integral part of multifactorial therapy) reduces cardiovascular disease (CVD) for longer term, both in type 1 and type 2 diabetes. In particular, cardiovascular events are reduced by approximately 10-15% per 1% absolute reduction of HbA1c, on top of other CVD-risk-reducing therapies. With regard to mortality, the situation is less clear, as those intervention studies need at least a 10-year follow-up. In fact, some risks involved with blood-glucose-lowering therapy, for example, hypoglycaemia and weight gain, especially in patients with prior CVD, may also impact unfavourably on (cardiovascular) mortality. Therefore, blood glucose lowering is a highly individualised therapy with a target for HbA1c <or=7.0% or 6.5%, which takes time to tailor (poly-)pharmacotherapy gently to the patient's needs. Drug-specific effects, both advantageous and disadvantageous, of blood-glucose-lowering therapy cannot be excluded currently and warrant further studies.