Human prion diseases, though relatively rare, remain an ongoing public health problem. They are fatal diseases, with unconventional host responses and no early diagnostic tests or robust treatments. Public health measures were put in place to protect the food chain in the United Kingdom from the late 1980s, with similar measures following elsewhere. However, human prion diseases are transmissible through other routes, including through blood transfusion and surgery. As a result, the public health threat remains for all forms of human prion diseases and makes continued surveillance and infection prevention and control imperative.