The progressive supranuclear palsy (PSP) is a rapidly progressing degenerative disease belonging to the family of tauophaties, characterized by the involvement of both cortical and subcortical structures. Although the pathogenesis of PSP is still uncertain, genetic, biochemical, and immunohistochemical studies have been performed and are reviewed here. Genetic factors, oxidative damage, neurotoxins, and environmental factors contribute to tau deposition in the cerebral areas involved in PSP. Symptoms originate from the ensuing dysfunction of dopaminergic, GABAergic, cholinergic, and noradrenergic pathways. Recent advances in neuroradiological and instrumental examinations facilitate the diagnosis and have gained new insights into the pathophysiology of PSP, although the primary cause of the disease is unknown and disease-modifying drugs are not yet available.