This chapter states that it is necessary to take an overview of the factors involved in etiology of multiple sclerosis (MS) and to formulate a general hypothesis, before specific etiological agents are considered. Electrophoresis of the cerebral spinal fluid (CSF) shows the presence of oligoclonal bands of immunoglobulin in MS patients, although this is only diagnostic in conjunction with other criteria and magnetic resonance imaging (MRI). Most studies have concentrated on identifying virus infection as the trigger for MS. MS is more common in White people than in other racial groups, and is also common in women than men. Evidence for a genetic basis for MS susceptibility has been obtained by studying the association between MS and alleles of the multiple histocompatibility complex. Detailed studies of the pathology of MS lesions from a large number of patients indicate that a number of different mechanisms of demyelination may be operated.