Prion diseases are degenerative disorders of the nervous system caused by transmissible particles that contain a pathogenic isoform of the prion protein, a normal constituent of cell membranes. The most common human prion disease is Creutzfeldt-Jakob disease (CJD). Most cases are sporadic with unknown mode of transmission, 10–15% of cases are inherited, and a small number have been transmitted by medical procedures. The spread of human prion diseases through consumption of infected material has been implicated historically in kuru and recently in variant CJD. Animal prion diseases (scrapie of sheep, transmissible mink encephalopathy, chronic wasting disease of cervids, and bovine spongiform encephalopathy) all seem to be laterally transmitted by contact with infected animals or by consumption of infected feed. The different modes of transmission of different prion diseases, the unpredictable species barriers, the variable distribution of infectivity in tissues, and strain variations found in some diseases all make risk assessment and predictions of future events difficult.