AbstractMultiple sclerosis (MS) is characterized by the active degradation of central nervous system myelin, a multilamellar membrane system that insulates nerve axons. MS arises from complex interactions between genetic, immunological, infective, and biochemical mechanisms. Although the circumstances of MS etiology remain hypothetical, one persistent theme involves immune system recognition of myelin-specific antigens derived from myelin basic protein, the most abundant extrinsic myelin membrane protein, and/or another equally suitable myelin protein or lipid. Knowledge of the biochemical and physical-chemical properties of myelin proteins, and lipids, particularly their composition, organization, structure, and accessibility with respect to the compacted myelin multilayers, thus becomes central to understanding how and why these antigens become selected during the development of MS. This article focuses on the current understanding of the molecular basis of MS as it may relate to the protein and lipid components of myelin, which dictate myelin morphology on the basis of protein-lipid and lipid-lipid interactions, and the relationship, if any, between the protein/lipid components and the destruction of myelin in pathological situations.