The renin–angiotensin–aldosterone system (RAAS) consists of bioactive angiotensin peptides, enzymatic pathways, receptors, and the steroid hormone aldosterone. The RAAS regulates blood pressure, sodium, and electrolyte homeostasis and mediates pathologic disease processes. Within this system is an alternative arm that counterbalances the vasoconstrictive, sodium and water retentive, and pro-fibrotic and inflammatory effects of the classical arm. Improved biochemical methodologies in RAAS quantification are elucidating how this complex system changes in health and disease. Future treatments for cardiovascular and kidney disease will likely involve a more nuanced manipulation of this system rather than simple blockade.