Technical Abstract: A prion is an infectious isoform of a natural cellular protein. It is the cause of a set of invariably fatal transmittable neurodegenerative diseases, transmissible spongiform encephalopathies (TSEs). TSEs include scrapie, Kuru, bovine spongiform encephalopathy (BSE) and Creutzfeld-Jakob Disease (CJD). With the exception of scrapie, all of these diseases were first described in the 20th century. The infectious isoform induces the conversion of natural isoform to the infectious isoform, resulting in a propagation of the infection throughout the susceptible tissues of the host. An infectious dose (ID50) is estimated at between 105 to 106 molecules. Unlike the normal isoform, infectious prions are very stable molecules. They persist in the environment for years and are resistant to autoclaving. Fields grazed by infected animals will remain infectious for years. Prions possess the worst properties of persistent toxins and virulent pathogens. This presentation will include a historical review of how an obscure sheep pathology lead to the discovery of prions and why a seemingly unimportant disease of U.K. cattle became the mad cow scare. It will highlight current research on structure, detection and pathology of the infectious isoform. It will discuss the differences and consequences of BSE and chronic wasting disease (CWD), an emerging TSE of wild and farm-raised deer and elk.