Since the discovery of renin by Tigerstedt in 1898, the complex roles of the components of the renin angiotensin system (RAS)have been extensively studied. RAS is involved in maintaining the homeostasis of body fluids and thus regulates the blood pressure.Renin is the key regulatory enzyme of RAS that catalyzes its only substrate angiotensinogen into the decapeptide angiotensin I,which is then converted into the octapeptide angiotensin II by angiotensin converting enzyme. Angiotensin II exerts its physiologicaleffects through angiotensin type 1 and type 2 receptors. Elucidation of the three-dimensional structure of renin has led to the designand synthesis of several synthetic peptides that inhibit renin activity, controlling blood pressure. Nephrectomized animals haveno detectable level of renin in their blood plasma, indicating that the kidney is the only source of renin. Renin is synthesized aspreprorenin, which is processed into prorenin. Prorenin is the preactive form of renin, with an extra 43 amino acid residues that blockthe active site of renin. Prorenin can be converted into renin proteolytically by the action of trypsin, cathepsin, and other proteases.However, non-proteolytically activated prorenin (using acidic pH, low temperature, or protein-protein interactions) is also possible,resulting in enzymatically active renin. The (pro)renin receptor [(P)RR], a RAS member, activates prorenin through protein–proteininteractions and exhibits angiotensin II-dependent as well as angiotensin II-independent functions. (P)RR in conjunction with (pro)reninexerts pathophysiological activities in human and animal models, especially in end-stage organ damage. Design of peptides that mimicparts of renin/prorenin can help to explain the binding interaction between (P)RR and its ligands. This article includes a discussion ofthe complex current challenges of studying renin, prorenin, and (P)RR.