Seven aquaporin water channels are expressed in human kidneys, and they have key roles in maintaining body water homeostasis. Impairment of their function can result in nephrogenic diabetes insipidus and other water-balance disorders. A lot of data have increased understanding of the functions and mechanisms of regulation of aquaporins both at the molecular and the clinical level. Research has also focused on aquaporins as therapeutic targets. This Review describes recent progress in uncovering the physiology and pathophysiology of aquaporins in the kidney, with particular attention devoted to AQP2, the most well-studied member of this protein group.