The family of illnesses called transmissible spongiform encephalopathies (TSEs), or "prion" diseases, is composed of a small number of human and animal neurodegenerative diseases caused by unique pathogenic agents that are still not fully defined. They are best considered as "protein-misfolding diseases" (together with Alzheimer's disease, Parkinson's disease, and a few other rare examples) resulting from the conversion of a normal body protein into a misfolded amyloid multimer. The pathogenic agents display a unique resistance to conventional disinfection methods and an extraordinary environmental durability, which has led the US Department of Agriculture to designate the causative agent of bovine spongiform encephalopathy as a bioterrorism security threat. In this review, precautions and regulations concerning the handling of TSE agents are discussed in relation to personnel and environmental biosafety.