In this review, we emphasize neuropathologic and neurobehavioral aspects of central pontine and extrapontine myelinolysis (CPM/EPM), also known as the osmotic demyelination syndrome. The literature is reviewed from the time of the initial report in 1959 and from key developments that have occurred more recently. Particular consideration is given to pathogenic mechanisms as revealed by recent animal studies. The role of white matter pathology in neurobehavioral dysfunction is also considered. The "then" and "now" of CPM and EPM tell 2 different stories. Yet, in many respects, this expansion of information over the past nearly 50 years simply represents a continuum, as well as recognition, of the vast gaps that still persist in our understanding of this disorder.