The critical role played by the renin–angiotensin–aldosterone system (RAAS) in the regulation of blood pressure and body fluid homeostasis has been well recognized. Angiotensin (Ang) II and aldosterone are the most powerful biologically active products of the RAAS, although there are also other bioactive Ang peptides involved in this system, including AngIII, AngIV, and Ang1 – 7. In addition to their physiological roles, AngII and aldosterone induce inflammation, cell growth, mitogenesis, apoptosis, migration, and differentiation; regulate gene expression of bioactive substances; and activate multiple intracellular signaling pathways, all of which contribute to cardiovascular tissue injury. During the last decade, both clinical and preclinical studies have demonstrated that various pharmacological interventions of the RAAS exert blood pressure–independent cardiovascular-protective effects. In this Forum Minireview entitled “New approaches to blockade of the renin–angiotensin–aldosterone system”, we will discuss the impact of RAAS inhibitors on prevention of the development of hypertension and cardiovascular diseases. Before going into details about the insights into RAAS inhibition that each of the four groups will provide, we herein briefly overview our current understanding of regulation of the circulating RAAS.