The renin-angiotensin system (RAS) is one of important systems among homeostatic mechanisms that control the function of cardiovascular, renal and adrenal systems. As RAS has a very complex nature, it has been also found as related to the control of cell migration and apoptosis. Angiotensin-converting enzyme inhibitors (ACEI) are drugs most commonly used in the modulation of RAS activity. ACEI have been extensively described as effective in the treatment of hypertension among adults, but also as drugs delaying progression in diabetic nephropathy and reducing mortality in left ventricular dysfunction and congestive heart failure. What is less obvious, ACEI are also widely used in pediatric nephrology and cardiology. Moreover, there are more and more reports showing evidence that ACEI can be beneficial in the treatment of many other diseases and the pleiotropic activity of ACEI is mainly based on their antioxidant properties. In this paper we focus on the less obvious possibilities of the clinical use of ACEI in neurological or oncological patients, discuss the role of ACE gene polymorphism and show the perspectives of potentially new applications of ACEI in contemporary pharmacotherapy.