The development of diabetic nephropathy exaggerates the cardiovascular risks in patients with diabetes types 1 and 2. Therefore, preventing or at least decelerating the progression of renal lesions has an enormous clinical and socio-economic impact. Besides the control of hyperglycemia, antihypertensive therapy with a blood pressure goal of below 130/80 mmHg is mandatory. The blockade of tissue derived renin-angiotensin-systems with ACE-inhibitors or AT-1-receptor-antagonists is highly effective. Nephroprotective as well as cardioprotective effects have been shown in a variety of large clinical trials. Pathophysiological considerations would support a combination therapy, however, so far there is a lack of valid clinical data. With regard to diabetic nephropathy, an early multifactorial approach, including patient education as well as medical therapy, offers the best chance of avoiding this serious complication with its associated medical risks.