In 1969, Graham and Oppenheimer introduced the term multiple systematrophy (MSA) to denote a neurodegenerative disease characterized clinicallyby varying combinations of autonomic, parkinsonian, cerebellar or pyramidalsymptoms or signs, and neuropathologically by cell loss and gliosis in the basalganglia and olivopontocerebellar system. They deserve recognition for havingidentified as a single entity a disease that previously had been reported underthe rubrics of olivopontocerebellar atrophy, idiopathic orthostatic hypotension,Shy-Drager syndrome and striatonigral degeneration depending upon the clin-ical presentation.This special issue of Journal of Neural Transmission contains the invitedlectures presented as part of the Second International Meeting on MSA in Romeon June 17–18, 2004. This meeting followed a previous one dedicated to thischallenging neurodegenerative disease that had been held in London in 1997.Since the meeting of investigators concerned with MSA in 1997, severalnew advances in our understanding of the cellular pathology and clinical fea-tures of MSA have been reported. In the late nineties a-synuclein was re-cognized as a major component of glial cytoplasmic inclusions (GCIs), whichrepresent the specific inclusion pathology found in the brain of patients withMSA regardless of clinical presentation (Spillantini et al., 1998). Based uponthese developments in molecular pathogenesis, MSA has been firmly estab-lished as a-synucleinopathy along with Parkinson’s disease and dementia withLewy bodies.In parallel with improved understanding of molecular pathogenesis, recog-nition of MSA as a clinical entity greatly improved following the introductionof new diagnostic criteria. Quinn first proposed in 1989 a list of diagnosticcriteria (Quinn, 1989). He divided MSA patients into two major categories:those presenting with predominantly parkinsonian signs (‘‘MSA-SND’’) andthose with predominant cerebellar involvement (‘‘MSA-OPCA’’). Within eachof these groups patients were labelled as clinically possible or probable accord-ing to the extent to which multiple systems were involved. Cases were classifiedas definite only when neuropathological confirmation was obtained. These