Gerstmann-Sträussler-Scheinker (GSS) is a slowly progressive hereditary autosomal dominant disease (OMIM: 137440) and the first human transmissible spongiform encephalopathy (TSE) in which a mutation in a gene encoding for prion protein (PrP) was discovered. The first "H" family had been known by the Viennese neuropsychiatrists since the XXth century and was reported by Gerstmann, Sträussler and Scheinker in 1936. In this chapter we present the clinical, neuropathological and molecular data on GSS with the mutations in the PRNP gene: at codons 102, 105, 117, 131, 145, 187, 198, 202, 212, 217 and 232. In several families with GSS the responsible mutations are unknown.