Role of ACE, ACE2 and Neprilysin in the Kidney -- ACE Inhibition in Heart Failure and Ischaemic Heart Disease -- Proteases of the Renin-Angiotensin System in Human Acute Pancreatitis -- The Renin-Angiotensin System in Pancreatic Stellate Cells: Implications in the Development and Progression of Type 2 Diabetes Mellitus -- Renin-Angiotensin System Proteases and the Cardiometabolic Syndrome: Pathophysiological, Clinical and Therapeutic Implications -- The Role of the Renin-Angiotensin System in Hepatic Fibrosis -- The Renin-Angiotensin System in the Breast -- Role of Local Renin-Angiotensin System in the Carotid Body and in Diseases -- Bone Homeostasis: An Emerging Role for the Renin-Angiotensin System -- The Renin-Angiotensin System and its Inhibitors in Human Cancers -- The Skeletal Muscle RAS in Health and Disease -- Local Angiotensin Generation and AT2 Receptor Activation -- ADAMs as Mediators of Angiotensin II Actions. The circulating renin-angiotensin system (RAS) is a hormonal system that regulates blood pressure, electrolyte and fluid homeostasis. Angiotensin II (Ang II), along with bioactive peptides such as Ang III, Ang IV and Ang (1-7) are the main effector peptides of the RAS. These peptides are the products of the proteolytic actions of renin, angiotensin-converting enzyme (ACE), ACE-2, and other angiotens- processing peptidases. Such angiotensin peptides exert their functions through their respective angiotensin receptors, namely AT1, AT2, AT4 and AT7 receptors. In the past decade, it has been recognized that numerous tissues and organs express their own RAS components and peptide activities. Such intrinsic systems are particularly suited for providing autocrine, paracrine or intracrine pathways having local functions that are different from, complementary to and, in some situations even counteracting, the circulating RAS. These local functions include, but are not limited to, cell growth, anti-proliferation, apoptosis, generation of reactive oxygen species, fibrogenesis, hormonal secretion, and vascular tone. The targets of these actions extend beyond the established nervous and cardiovascular systems, and now reach such diverse targets as the bone tissue, carotid body, adipose and liver tissues, and the pancreas. Additionally, local RAS are subject to regulation by various physiological and pathophysiological conditions. Blockade of the RAS thus has the potential to provide extensive and novel strategies for alternative approaches in the treatment of cardiovascular, renal, hepatic, skeletal and pancreatic diseases.