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This update discusses novel aspects on clinicopathological concepts and therapeutic challenges in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), arising from publications of the last 1.5 years.The clinical criteria for diagnosis of PSP have been revised. Clinical variability of pathologically defined PSP and MSA makes the development of mature biomarkers for early diagnosis and biomarker-based trial design indispensable. Novel molecular techniques for biomarker supported diagnosis of PSP and MSA and for monitoring disease progression are being studied. Research in the pathophysiology of both diseases generates gradual progress in the understanding of the underlying processes. Several promising disease-modifying therapeutic approaches for PSP and MSA are now moving into clinical trials.Recent research generates insights in the pathophysiological relevant processes and raises hope for earlier clinical diagnosis and disease-modifying therapies of patients with PSP and MSA.