Although multiple sclerosis is generally believed to be a T-cell mediated inflammatory disease of the central nervous system, recent experimental and neuropathological studies show that additional pathogenetic factors are required to induce widespread primary demyelination and secondary tissue damage, such as axonal loss. This review summarises experimental evidence for multiple pathogenetic pathways, that can be responsible for myelin destruction in this disease. Furthermore, recent data are discussed which show that different immunopathological pathways seem to be involved in different patient subgroups. The pathogenetic heterogeneity of multiple sclerosis suggests that immunomodulatory treatment of this disease may be more complex than previously anticipated.