OBJECTIVES: Progressive supranuclear palsy (PSP) is a rare neurological disease that is characterized by a primary tau pathology. PSP symptoms include early and severe gait instability with falls, slowing of vertical saccadic eye movements, slowed movement, rigidity of the axial musculature, dysphagia, dysarthria, pseudobulbar affect, neuropsychiatric abnormalities, and dementia. There are currently no available treatments for patients with PSP. The objective of this research was to review the available evidence on humanistic and economic burden of PSP, as a foundation work for understanding the unmet needs of this population. METHODS: A systematic literature review was conducted in 9 databases including Medline and Embase in 2000-2017, supplemented with hand searches of reference lists. Where available, PSP Richardson syndrome (PSP-RS) and other phenotypes were assessed. RESULTS: Health utility (as reported by EQ5D) was measured in 5 studies with a mean utility ranging 0.20-0.41 after mean disease duration of 4.7-6.1 years. PSP patients had the most difficulties with usual activities followed by mobility and self-care. Four studies investigated the gradual worsening of daily activities in the Schwab and England Activities of Daily Living (SEADL) scale and described fast disease progression (annual worsening exceeded 10 points on the 100-point scale). Annual worsening in Clinical Global Impression (CGI) was in the 0.7-0.9 range. Healthcare resource utilization was reported in 5 studies, describing wheelchair dependence, urinary catheterization, tube feeding, hospitalizations, and residential care as important cost drivers. PSP patients typically receive informal care from family members who experienced high psychological strains. CONCLUSIONS: Most PSP studies report severely diminished quality of life with rapidly worsening functions. Humanistic and economic burden by PSP disease states or progression levels should be further investigated, to allow subsequent development of health economic models for the value assessment of emerging treatments promising slower PSP progression.