The aetiology proposed for the development of chronic cerebrospinal venous insufficiency (CCSVI) associated with multiple sclerosis (MS) has been the presence of congenital truncular venous malformations. However, this hypothesis is not consistent with the epidemiology or geographical incidence of MS and is not consistent with many of the ultrasonographic or radiographical findings of the venous disturbances found in MS patients. However, the probability of a venous aetiology of MS remains strong based on evidence accumulated from the time the disorder was first described. The method used in this review was to search PubMed for all past medical publications related to vascular, venous, haematological, epidemiological, biochemical, and genetic investigations and treatments of MS. Epidemiological and geographical findings of prevalence of MS indicate the involvement of an infective agent. This review of the venous pathology associated with MS describes a hypothesis that the pathogenesis of the venous disease could be initiated by a respiratory infective agent such as Chlamydophila pneumonia, which causes a specific chronic persistent venulitis affecting the cerebrospinal venous system. Secondary spread of the agent would initially be via the lymphatic system to specifically involve the azygos, internal jugular and vertebral veins. The hypothesis proposes mechanisms by which an infective venous vasculitis could result in the specific neural damage, metabolic, immunological and vascular effects observed in MS. The hypothesis described is consistent with many of the known facts of MS pathogenesis and therefore provides a framework for further research into a venous aetiology for the disease. If MS does result from a chronic infective venulitis rather than a syndrome involving congenital truncular venous malformations, then additional therapies to the currently used angioplasties will be required to optimize results.