Central pontine myelinolysis (CPM) is a demyelinating condition affecting not only the pontine base, but also involving other brain areas. It usually occurs on a background of chronic systemic illness, and is commonly observed in individuals with alcoholism, malnutrition and liver disease. Studies carried out 25-30 years ago established that the principal etiological factor was the rapid correction of hyponatremia resulting in osmotic stress. This article reviews progress achieved since that time on its pathogenesis, focusing on the role of organic osmolytes, the blood-brain, barrier, endothelial cells, myelinotoxic factors triggered by osmotic stress, and the role of various factors that predispose to the development of CPM. These advances show great promise in providing novel therapeutic options for the management of patients afflicted with CPM.