Recent studies suggest that water drinking elicits acute changes in human physiology. Water drinking profoundly increases blood pressure in patients with autonomic failure. Water drinking also increases blood pressure in quadriplegic patients, cardiac transplant recipients, and older healthy subjects, but to a lesser extent. Blood pressure does not change in healthy young subjects. More recently, water drinking was shown to increase energy expenditure. The acute changes in cardiovascular regulation and in energy expenditure with water drinking appear to be mediated through activation of the sympathetic nervous system. The sympathetic activation may involve a spinal reflex-like mechanism. The stimulus that causes the sympathetic activation is not known. The acute water pressor response can be exploited in the treatment of patients with impaired orthostatic tolerance caused by autonomic failure, postural tachycardia syndrome, or, perhaps, neurocardiogenic (vasovagal) syncope. The increase in energy expenditure with water drinking should be recognized as an important confounding variable in metabolic studies and may hold some promise as an adjunctive measure in the prevention or treatment of obesity.