D iabetes is a growing disease with a potentially devastating outcome. Diabetic patients run a great risk of developing multiple organ dysfunction and ultimately organ failure. The current approach of patients with diabetes is first to assess their risk profile by measuring risk factors such as glucose level, systemic blood pressure, blood lipids, body weight, and smoking. Second, to reduce the risk, the patient is advised to make a lifestyle change (lose weight and stop smoking) and to take medication that regulates glucose and lowers blood pressure and cholesterol. This approach has indeed resulted in a slowing of progressive organ dysfunction and has substantially prolonged life. However, the residual risk of diabetic patients, despite “optimal” treatment of these risk factors, is still extremely high, and the number of patients is dramatically growing. This has urged the medical profession to improve risk profiling and design new therapeutic strategies to further reduce existing risk. In addition, the search for early disease markers was intensified with the goal to apply preventive therapeutic measures in early stages of disease, instead of waiting until the disease had fully developed. The next paragraphs will address the status of a “new” cardiovascular and renal risk marker: increased levels of albumin in the urine. This so-called albuminuria not only marks risk in advanced stages of diabetic disease, but also indicates risk in the very early stages of the disease. Moreover, new antihypertensive therapies not only lower blood pressure, but also reduce albuminuria. We will address the need of not only measuring the risk marker, but also targeting therapies to lower albuminuria. Finally, the individual response to such therapies appears to be highly variable, offering us opportunities to optimize organ protection by individualizing therapies with the goal to overcome therapy resistance. Clearly, diabetes constitutes a multifactorial disease in its organ damage (and maybe even in its cause). This forms a sound reason to look for multiple targets (next to optimization of treating existing targets).