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Background: Multiple system atrophy (MSA) is considered a progressive α-synuclein pathology characterized by autonomic failure, parkinsonism, and cerebellar dysfunction. Owing to its clinical heterogeneity and overlap with other neurodegenerative disorders, accurate diagnosis remains challenging. Diagnostic criteria have evolved substantially over the past three decades in response to advances in neuropathology, neuroimaging, autonomic testing, and clinicopathological validation. Methods: A narrative historical review was conducted examining the evolution of MSA diagnostic criteria from the Quinn criteria (1989) to the 2022 Movement Disorder Society (MDS) criteria. Major diagnostic frameworks, including the revised Quinn criteria, First and Second Consensus Criteria, NNIPPS criteria, and Japanese MSA criteria, were reviewed alongside key studies evaluating diagnostic accuracy, clinicopathological validation, and emerging biomarkers. Results: The Quinn criteria provided the first formal framework for MSA diagnosis, while subsequent criteria improved standardization through refined definitions of autonomic failure, phenotypic classification, supportive neuroimaging features, and evidence-based diagnostic thresholds. Regional and research-based initiatives contributed additional insights into disease heterogeneity and diagnostic performance. The 2022 MDS criteria introduced clinically established, clinically probable, and possible prodromal MSA categories and formally incorporated characteristic MRI findings into the diagnostic process. Despite these advances, early diagnosis remains difficult, and neuropathological confirmation continues to represent the diagnostic gold standard. Conclusions: The evolution of MSA diagnostic criteria reflects a transition from descriptive clinical classi-fication toward increasingly objective and biologically informed diagnosis. Future re-finements will likely integrate molecular biomarkers and advanced imaging techniques, facilitating earlier diagnosis, improving patient selection for clinical trials, and supporting the development of disease-modifying therapies.
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