Healthy kidneys maintain fluid and electrolyte homoeostasis by adjusting urine volume and composition according to physiological needs. The final urine composition is determined in the last tubular segment: the collecting duct. Water permeability in the collecting duct is regulated by arginine vasopressin (AVP). Secretion of AVP from the neurohypophysis is regulated by a complex signalling network that involves osmosensors, barosensors and volume sensors. AVP facilitates aquaporin (AQP)-mediated water reabsorption via activation of the vasopressin V2 receptor (AVPR2) in the collecting duct, thus enabling concentration of urine. In nephrogenic diabetes insipidus (NDI), inability of the kidneys to respond to AVP results in functional AQP deficiency. Consequently, affected patients have constant diuresis, resulting in large volumes of dilute urine. Primary forms of NDI result from mutations in the genes that encode the key proteins AVPR2 and AQP2, whereas secondary forms are associated with biochemical abnormalities, obstructive uropathy or the use of certain medications, particularly lithium. Treatment of the disease is informed by identification of the underlying cause. Here we review the clinical aspects and diagnosis of NDI, the various aetiologies, current treatment options and potential future developments.