Recent research has led to the discovery of potent selective or mixed endothelin-converting enzyme (ECE), ECE/neutral endopeptidase24.11 (NEP) and ECE/NEP24.11/angiotensin-converting enzyme (ACE) inhibitors. There is also increasing evidence, that the functions of the endothelin (ET), renin-angiotensin and NEP systems for the regulation of the cardiovascular homeostasis are connected by a complex regulation network. It will be the challenging task of future research with the newly available selective and mixed ECE-1 inhibitors to show whether the combined inhibition of more than one cardiovascular system is superior to selective inhibition.