Mammalian prions are unique pathogens and are composed of infectious polymeric assemblies of misfolded host-encoded prion protein which propagate by means of seeded protein polymerization. Different prion strains can propagate in the same host to produce different disease phenotypes and appear to be encoded by distinct pathogenic prion protein conformations and assembly states. Although historically rare in humans, the appearance of variant Creutzfeldt-Jakob disease (vCJD) in the UK from 1995 onwards, and the experimental confirmation that this was caused by dietary or other exposure to bovine spongiform encephalopathy (BSE) prions from cattle, has led to intense efforts to understand the fundamental details of prion pathogenesis in order to protect public health and to develop rational therapeutics.