Multiple system atrophy is an adult-onset, sporadic, and progressive neurodegenerative disease. People with this disorder report a wide range of motor and non-motor symptoms. Overlap in the clinical presentation of multiple system atrophy with other movement disorders (eg, Parkinson’s disease and progressive supranuclear palsy) is a concern for accurate and timely diagnosis. Over the past 5 years, progress has been made in understanding key pathophysiological events in multiple system atrophy, including the seeding of α-synuclein inclusions and the detection of disease-specific α-synuclein strains.