A series of recently published articles by a group of Austrian, German and American neuropathologists have proposed the existence of several different pathogenetic pathways in multiple sclerosis (MS). These studies were based on both biopsy and autopsy material. A review of the available published clinical, imaging and cerebrospinal fluid data suggest that some the cases used in those studies were more probably instances of disseminated encephalomyelitis rather than MS. This has serious implications regarding the specificity and significance of the findings in regard to MS pathogenesis. The specific myelinoclastic sequence and the variable clinical course of MS are determined by the individual's genetic endowment and immunologic history. Regardless of pathogenetic pathway and clinical course, the final pathologic picture of MS is always the same. The MS brain is genetically programmed to produce a unique, pathognomonic change, the plaque with sharply demarcated borders.