Multiple system atrophy (MSA) is a sporadic and rapidly progressive neurodegenerative disorder that presents with autonomic failure in combination with parkinsonism or cerebellar ataxia. Over the past 5 years, substantial progress has been achieved in understanding the pathogenesis of the disease. Important insights into the epidemiology and genetics of MSA have confirmed the key pathogenic role of alpha-synuclein. Advances in the early recognition of this disease have resulted in revised diagnostic criteria, including, for the first time, neuroimaging indices. Finally, novel therapeutic options targeting disease modification have been investigated in clinical trials. These include riluzole, recombinant human growth hormone, and minocycline. Although the trials did not find any positive effects on disease progression, they generated important trial expertise in MSA and were only possible because of the establishment of international networks.