Correct physiological function of all the systems in the body requires a constant supply of water and sodium, and this is particularly so for the cardiovascular system. The physiological regulation of body fluids is ensured by the mechanisms of thirst and of sodium appetite, which maintain plasma volume and osmolality within set limits by initiating ingestive behaviors for water and sodium as well as the release of hormones to conserve them within the body. There are 2 major fluid compartments in this regulation: intracellular and extracellular (blood). An increased blood osmolality draws water from cells into the blood, thus dehydrating specific brain osmoreceptors that stimulate drinking and release of antidiuretic hormone (ADH or vasopressin). Antidiuretic hormone via specific receptors in the kidney reduces water loss by lowering urine volume. Extracellular dehydration (hypovolemia) stimulates specific receptors that signal brain centers to initiate drinking and ADH release. Baroreceptors/volume receptors in the kidney release the enzyme renin, which via a well-known cascade leads to the production of angiotensin II (AngII), which stimulates also drinking and ADH release. Angiotensin II and a lowered blood volume stimulate also the release of aldosterone to reduce kidney loss of urine sodium. Water and sodium intake return osmolality and volume to the required levels, thus ensuring that the cardiovascular system maintains a constant perfusion pressure to all cells and organs of the body. If drinking does not take place or not enough is consumed, then ADH, AngII, and aldosterone will continue to be released. Treatment of cardiovascular disease uses medications designed to antagonize the renin-AngII-aldosterone system, which suggests that hypohydration, or more specifically hypovolemia, makes up a large part of the etiology of this serious health problem.