<p>Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by cerebellar dysfunction, a Parkinsonian syndrome with poor response to levodopa and autonomic failure. The diagnosis of MSA is particularly challenging in its early stages due to symptom overlap with other neurodegenerative Parkinson syndromes. Recent advances in neuroimaging have greatly improved the accuracy of the diagnosis in clinical routine and provided valuable insights into the pathophysiology and progression of MSA. Macrostructural MRI shows atrophy in regions such as the putamen and pontocerebellar regions, distinguishing MSA from other Parkinson syndromes. Advanced imaging techniques, including diffusion tensor imaging (DTI), free water imaging and quantitative susceptibility mapping, add further value in assessing disease progression. While dopamine transporter (DAT) imaging is the mainstay for confirmation of nigrostriatal degeneration in suspected neurodegenerative Parkinson syndromes and may enable to identify prodromal cases, cardiac sympathetic imaging with [123I]MIBG scintigraphy may be used for delineation of MSA from Parkinson’s disease (PD). Positron emission tomography (PET) with the glucose analogue [¹⁸F]FDG depicts disease-specific metabolic patterns in MSA and various neurodegenerative diseases, which do not only enable a highly accurate differential diagnosis of MSA (e.g., from PD and other atypical Parkinson syndromes) but also carry important prognostic and pathophysiological information. Various other PET radiopharmaceuticals currently under investigation in MSA provide novel insights into neurotransmitter system changes, glial pathology and, most recently, α-synuclein pathology. These imaging modalities considerably expand the diagnostic and prognostic capabilities in MSA and may provide important biomarkers for tracking disease development, progression and treatment.</p>