The second consensus statement on the diagnosis of multiple system atrophy (MSA) was developed following a 2-day consensus conference in 2007. The new criteria retain the diagnostic categories of MSA with predominant parkinsonism (MSA-P) and MSA with predominant cerebellar ataxia (MSA-C), as well as the designations of definite, probable, and possible MSA. Definite MSA requires neuropathologic demonstration of α-synuclein-positive glial cytoplasmic inclusions in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Probable MSA requires a sporadic, progressive adult-onset disorder with autonomic failure and either poorly levodopa-responsive parkinsonism or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult-onset disease with parkinsonism or cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus one other feature that may be clinical or neuroimaging abnormality. The new criteria simplify the previous ones, incorporate current knowledge, and are expected to enhance future assessments of the disease. The criteria emphasize the importance of autonomic dysfunction in the diagnosis of MSA. The diagnosis of probable MSA requires a reduction in systolic or diastolic blood pressure after standing, with a compensatory increase in heart rate that is inadequate for the level of blood pressure decline. Autonomic failure is a key feature of MSA, and its evaluation includes clinical history, orthostatic blood pressure measurements, and comprehensive tests for cardiovascular, sudomotor, and urinary deficits. Parkinsonism in MSA is characterized by bradykinesia, rigidity, tremor, and postural instability, but typically responds poorly to levodopa therapy. Cerebellar ataxia is a common feature in MSA-C, and its diagnosis involves assessing gait, speech, and oculomotor function. Imaging techniques such as MRI and PET can help differentiate MSA from other conditions. The new criteria also address the differential diagnosis of adult-onset cerebellar ataxia, including spinocerebellar ataxias and fragile X-associated tremor/ataxia syndrome. The new criteria are intended for both practicing clinical neurologists and investigators studying the disease. They aim to improve diagnostic accuracy and reduce false positives, particularly in the early stages of the disorder. The criteria are based on consensus methodology, which involves the collected experience of active investigators, but they do not result from an evidence-based approach. Future validation studies are expected to confirm the accuracy and sensitivity of the new criteria.The second consensus statement on the diagnosis of multiple system atrophy (MSA) was developed following a 2-day consensus conference in 2007. The new criteria retain the diagnostic categories of MSA with predominant parkinsonism (MSA-P) and MSA with predominant cerebellar ataxia (MSA-C), as well as the designations of definite, probable, and possible MSA. Definite MSA requires neuropathologic demonstration of α-synuclein-positive glial cytoplasmic inclusions in association with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Probable MSA requires a sporadic, progressive adult-onset disorder with autonomic failure and either poorly levodopa-responsive parkinsonism or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult-onset disease with parkinsonism or cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus one other feature that may be clinical or neuroimaging abnormality. The new criteria simplify the previous ones, incorporate current knowledge, and are expected to enhance future assessments of the disease. The criteria emphasize the importance of autonomic dysfunction in the diagnosis of MSA. The diagnosis of probable MSA requires a reduction in systolic or diastolic blood pressure after standing, with a compensatory increase in heart rate that is inadequate for the level of blood pressure decline. Autonomic failure is a key feature of MSA, and its evaluation includes clinical history, orthostatic blood pressure measurements, and comprehensive tests for cardiovascular, sudomotor, and urinary deficits. Parkinsonism in MSA is characterized by bradykinesia, rigidity, tremor, and postural instability, but typically responds poorly to levodopa therapy. Cerebellar ataxia is a common feature in MSA-C, and its diagnosis involves assessing gait, speech, and oculomotor function. Imaging techniques such as MRI and PET can help differentiate MSA from other conditions. The new criteria also address the differential diagnosis of adult-onset cerebellar ataxia, including spinocerebellar ataxias and fragile X-associated tremor/ataxia syndrome. The new criteria are intended for both practicing clinical neurologists and investigators studying the disease. They aim to improve diagnostic accuracy and reduce false positives, particularly in the early stages of the disorder. The criteria are based on consensus methodology, which involves the collected experience of active investigators, but they do not result from an evidence-based approach. Future validation studies are expected to confirm the accuracy and sensitivity of the new criteria.