For the human body to function optimally, the internal environment must be constant. The history and neuroanatomy was briefly explained in this chapter. Neurophysiology describes about control of secretion, neurotransmitters, osmoregulation, baroregulation, other regulatory mechanisms, and biological action of arginine vasopressin. The next topic discussed is diabetes insipidus (DI) also known as polyuria which is the excretion of copious urine, in excess of 3 L/24 hours. It is classified into hypothalamic DI (HDI), nephrogenic DI (NDI), gestational DI (GDI), dipsogenic DI (DDI), differential diagnosis, and the treatment options for HDI, NDI, GDI, and DDI are also discussed. This chapter also discusses the background, pathophysiology, etiology, diagnosis, cerebral salt wasting (CSW), and treatment for the syndrome of inappropriate antidiuresis (SIAD). The latter part of this chapter discusses about the newer developments in water homeostasis which includes vasopressin receptor antagonists— vaptans (aquaretics), and hypodipsia which includes definition and clinical characteristics; etiopathology and treatment.