Multiple sclerosis (MS) has recently been classified according to its clinical course. Despite relapses and remissions, its course is invariably progressive, and the observed progression from the remitting-relapsing to the secondary progressive form represents the accumulation of permanent damage to the nervous system. Discussions of the nomenclatural position of Schilder's, Marburg's, and Baló's diseases, ignore the fact that the unique, pathognomonic, sharp-edged plaque of MS, is also the pathologic end-result in the three variants. Devic's disease or neuromyelitis optica (NMO) is quite different and with some exceptions, is a particular form of disseminated encephalomyelitis (DEM). There is no evidence that the 'oriental form of MS' is anything but NMO. The suggestion that MS and DEM are variants of the same condition is contradicted by the fact that the pathological characteristics of the two are quite different. While it is probable that the two share aspects of pathogenesis, the patients differ because of their genetic endowment. This was dramatically demonstrated in a group of Japanese patients who died after anti-rabies vaccination and were found to have the typical sharp-edged lesions of MS. The genetic determinant was also crucial in the marmoset in which EAE uniquely resulted in a chronic relapsing-remitting (RR) disease characterized by the classic sharp-edged lesions of MS. The question 'ADEM: distinct disease or part of the MS spectrum?' can be answered with a resounding no. A new classification is proposed separating the different forms of MS from the various types of DEM.