© 2013 Springer Science+Business Media New York. All rights are reserved. Water is the most abundant constituent in the body. Vasopressin secretion, water ingestion, and the renal concentrating mechanism collaborate to maintain human body fluid osmolality nearly constant. Abnormalities in these processes cause hyponatremia, hypernatremia, and polyuria. The primary hormonal control of renal water excretion is by vasopressin (also named antidiuretic hormone). Thirst and vasopressin release from the posterior pituitary are under the control of osmoreceptive neurons in the central nervous system. The kidney maintains blood plasma osmolality and sodium concentration nearly constant by means of mechanisms that independently regulate water and sodium excretion. The renal medulla produces concentrated urine through the generation of an osmotic gradient extending from the cortico-medullary boundary to the inner medullary tip. This gradient is generated in the outer medulla by the countercurrent multiplication of a comparatively small transepithelial difference in osmotic pressure. This small difference, called a single effect, arises from active NaCl reabsorption from thick ascending limbs, which dilutes ascending limb flow relative to flow in vessels and other tubules. In the inner medulla, the gradient may also be generated by the countercurrent multiplication of a single effect, but the single effect has not been definitively identified. Continued experimental investigation and incorporation of the resulting information into mathematic simulations may help to more fully elucidate the inner medullary urine concentrating mechanism.