This review article discusses dental practice implications of prion diseases, including Creutzfeldt-Jakob disease. The current universal precautions used for infection control in dentistry do not inactivate infectious prions. There is a theoretical, yet real risk of prion disease transmission through dental treatment, although the magnitude of that risk has not yet been determined. Medical, family, and travel histories can demonstrate the need for implementing improved levels of infection control. Best practices include the following: For certain cases, single-use disposable dental instruments should be used. Those instruments that are not disposable, should have a thorough physical cleaning, be soaked in hot 1N sodium hydroxide solution for 1 hour, and then autoclaved in a vacuum or porous-load autoclave at 134°C to 138°C for 18 to 20 minutes. Dental and other health care professionals need to understand prion diseases, and for best practice, consider implementing recommended changes to infection-control measures, since current practices do not destroy infectious prions.