Angiotensin converting enzyme (ACE) has vital role in normal functioning of the human body due to its direct involvement in the renin-angiotensin-aldosterone system (RAAS), kinin-kallikrein system, in vitro degradation of amyloid beta-peptide, GPIase (glycosylphosphatidylinositol, GPI) activity and in signal transduction. As ACE activity level is strongly influenced by ACE insertion/deletion (I/D) polymorphism, a huge body of data has been generated to elucidate the association of I/D polymorphism with cardiovascular and non cardiovascular disea-ses like diabetes, diabetic nephropathy, diabetic retinopathy, atherosclerosis, coronary heart diseases and stro-ke, hypertension, Alzheimer’s disease, cancer and Parkinson’s disease. This review will be limited to the effect of ACE I/D polymorphism on longevity considering the pathophysiology of several diseases.