Sterilization of instruments and devices is a complex process; improperly processed instruments and devices can be very detrimental to patient safety. Success includes the education and effective participation of everyone who handles instruments from one point of use to the next, which includes the perioperative staff as well as those who work in the central sterile processing department. This article describes high-temperature sterilization and the various sterilizers available. Special focus is on sterilizing instruments that have come in contact with patients with Creutzfeldt-Jakob disease.