Prion diseases or transmissible spongiform encephalopathies are neurodegenerative disorders affecting a broad range of mammals including humans. Initially thought to be of viral origin, it became apparent that prion diseases are unique transmissible entities where a misfolded, highly stable conformer (PrPSc) of the host encoded prion protein (PrPC) represents an essential component of infectious "prions". Prion diseases are mainly studied in rodents, yet several scientific breakthroughs in prion research can be attributed to prion research in primates. In this review we summarize and discuss how studies in non-human primates have advanced our knowledge on transmissibility, pathophysiology and tissue tropism of prions. We discuss assets of non-human primate and rodent models of prion disease pointing out alternatives to experiments in primates.