Renal and cardiovascular complications make type 2 diabetes one of the most morbid conditions in medicine. The kidney frequently gets involved in this “multi-organ disease”. Of the large proportion of patients who progress with further loss of renal function, most prematurely die or end up in dialysis. Many interventions have targeted a decelerated progression of renal function loss, including metabolic control, blood pressure, and lipid management. Recently, modulation of the renin-angiotensin-aldosterone-system (RAAS) have been combined with the existing therapeutic armamentarium. RAAS inhibitors lower blood pressure and decrease albuminuria which leads to additionally protective renal and cardiovascular effects. Although this has been the success story of the last two decades, it has still made a relatively small contribution to patient welfare, since the residual risk in patients that received this optimal care remains extremely high. New treatment strategies are required that further slow the progression of renal and cardiovascular functions. Recently, several pathways have been investigated, targeting traditional risk factors such as blood pressure- and lipidlowering strategies with unexpected results. Furthermore, novel targets and drugs have been identified. Preliminary studies on surrogate markers for renal outcome show a great potential for additive renal protection, such that in many cases hard endpoint trials are initiated. Novel interventions, which are reviewed here, include vitamin D receptor activators, RAASi with direct renin inhibitors or aldosterone antagonists, endothelin-antagonist, inflammation suppression with pentoxyfillin, MCP-1 synthesis inhibitors, or with Nrf2 agonists. Despite the current depressing situation of type 2 diabetic patients with nephropathy, new treatment options are under development to reduce the high morbidity and mortality associated with this universal ever-increasing disease threat.