Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that usually manifests in the early sixth decade of life and progresses relentlessly with a mean survival of 9 years. Clinically, MSA is dominated by autonomic/urogenital failure, which may be associated with either levodopa (L-dopa) -unresponsive parkinsonism in 80% of cases (MSA-P subtype) or with cerebellar ataxia in 20% of cases (MSA-C subtype). Pathologically, MSA is characterized by a neuronal multisystem degeneration and abnormal glial cytoplasmic inclusions containing alpha-synuclein aggregates. Pharmacological treatment of motor features is disappointing except for a transient L-dopa response in a minority of MSA-P patients. In contrast, autonomic and urogenital features of MSA should be identified early on, because they can be treated effectively in many instances. Neuroprotective strategies are presently unavailable, however, two multicentre European trials have been launched to evaluate the effects of riluzole and human recombinant growth hormone on disease progression in MSA. Clearly, further randomised, controlled trials are required to identify effective symptomatic or neuroprotective agents in MSA. Several in vivo models have become available to allow a careful preselection of candidate agents. Several research groups have been formed in Europe (EMSA-SG, NNIPPS) and United States (NAMSA-SG), providing a framework for coordinated trial activity in MSA.