The existence of the renin-angiotensin-aldosterone system was first postulated over 100 years ago. Following the identification of all the major components, came the discovery of their potential pathogenicity in cardiovascular and renal disease. The introduction of drugs that inhibit the synthesis or actions of this system has prompted a number of trials that have largely shaped how cardiovascular and renal disease is managed today. The continued discovery of yet more components of this system promises to further our understanding of its influence on disease processes and herald the development of more highly selective drugs, ensuring that the renin-angiotensin-aldosterone system will continue to be a key area of interest for many years to come.