Previous research in end stage renal failure has focused on the renin-angiotensin-system. Today, we know, that in chronic renal failure sympathetic overactivity plays a pivotal role for progression of the disease and overall prognosis. The unique finding is that the damaged kidneys send afferent nerve impulses to the central nervous system to increase efferent sympathetic discharge. Systemically this sympathetic overactivity contributes to hypertension and associated cardiovascular complications. Locally in the kidney neurotransmitter release is enhanced, which induces proliferation thereby promoting loss of renal function. Consequently, it has been shown that pharmacological inhibition of sympathetic nerve activity prevents glomerulosclerosis and ameliorates proteinuria in models of chronic renal failure. Thus, the pathomechanism of sympathetic overactivity is likely to open a new therapeutic avenue for the treatment of hypertensive chronic renal failure patients.