The most important clinical feature of hyponatraemia is its effect on the central nervous system. It is crucial to be familiar with the pathophysiological concepts of hypotonic stress and the various defence mechanisms against it. In many cases, the signs and symptoms associated with hyponatraemia are mild and will go undiscovered by both physician and patient. In some situations, however, the complications are severe and may lead to irreversible damage to the brain. The time course as well as the magnitude of the decline of sodium levels determine the severity of symptoms. Development of hyponatraemia within less than 48 h is called acute hyponatraemia and is associated with a more severe clinical picture while chronic hyponatraemia is often less dramatic. In this chapter, the acute and chronic changes and perturbations of the central nervous system in hyponatraemia as well as their clinical presentation – summarized as hyponatraemic encephalopathy – will be reviewed.