Several well controlled multicenter trials demonstrated the great value of ACE-inhibitors in the treatment of heart failure. Interestingly, the mechanisms by which ACE-inhibitors improve survival of patients with heart failure are ony poorly understood. Interesting new aspects regarding the role of the renin angiotensin system in the pathophysiology of heart failure emerged from modern methods of molecular biology. For example, several alleles of the angiotensin converting enzyme or angiotensinogen genes were related to hypertension and myocardial infarction in both clinical and experimental studies. Furthermore, local renin angiotensin systems have been demonstrated in various cardiovascular tissues. These tissue renin angiotensin systems are independently regulated and may be activated in heart failure or cardiac hypertrophy. Finally, it has been shown that inhibition of angiotensin converting enzyme affects also the metabolism of bradykinin and aldosterone which may contribute to the overall pharmacodynamic profile of ACE-inhibitors in heart failure.