Our first insights into the pathogenesis of multiple sclerosis were obtained following developments in histopathology in the late 19th Century. More than a century later, despite the advanced molecular tools that are now available, significant progress in unravelling the pathogenesis of multiple sclerosis is still very much dependent on similar approaches. The inaccessibility of the CNS for direct study, and the clinical and genetic heterogeneity of multiple sclerosis combine to make the study of multiple sclerosis difficult to say the least (Compston et al., 1998). Recently Hans Lassmann and his colleagues Lucchinetti and Brück proposed a classification for multiple sclerosis lesions based on molecular histopathological findings from diagnostic biopsies and autopsies (Lassmann et al., 2001), an approach similar to that established by Prineas and Raine in the 1970s and ’80s (Raine et al., 1997). Lassmann’s patterns I–IV of demyelination and inflammation are not closely linked to specific relapsing–remitting or progressive disease courses, but may help us to understand the underlying immunological and/or neurodegenerative mechanisms involved in lesion formation. There is a pressing need to identify specific histopathological or paraclinical markers for the different pathogenic mechanisms that may be involved in multiple sclerosis. Only then will we be able to identify the most appropriate ‘customized’ therapeutic regimen for any individual patient using the growing repertoire of immunomodulatory and cytostatic drugs that are now available (Noseworthy et al., 2000).