Progressive supranuclear palsy (PSP) is the most common atypical neurodegenerative parkinsonian disorder (1,2). It was first described as a discrete clinicopathological entity by Steele et al. (3) in 1964 (Fig. 1), but there are several previous clinical descriptions of patients who may have had this disease (see Chapter 2). Clinically, PSP typically presents at middle-to-late age with progressive unexplained prominent postural instability with falls, supranuclear vertical gaze palsy, pseudobulbar palsy, levodopa-unresponsive parkinsonism, and frontal cognitive disturbances (3, 4, 5). Neuropathologically, PSP is characterized by the presence of neurofibrillary tangles in neurons and glia in specific basal ganglia and brainstem areas (6) (Fig.2). Neurofibrillary tangles are abnormal aggregates of tau protein that are also the main pathologic feature in corticobasal degeneration (CBD), Pick’s disease, frontotemporal dementia with parkinsonism associated to chromosome 17 abnormalities (FTDP-17), and Alzheimer’s disease (AD). Hence, as all these disorders, PSP is considered a “tauopathy” (see also Chapter 4).