The latest surge of the coronavirus disease 2019 (SARS-CoV-2 virus) pandemic continues to create an unprecedented need for mechanical ventilation in critically ill patients. The U.S. Food and Drug Administration (FDA) recognized that the additional need for ventilators, on March 22, 2020 and issued guidance outlining a policy intended to help increase availability of relevant technologies. The FDA included guidance for healthcare facilities facing shortages of mechanical ventilators to consider alternative devices capable of delivering breaths or pressure support including anesthesia machines. Anesthesia machine manufacturers have published guidelines for the off-label use of anesthesia machines in critical care settings. Capable of providing mechanical ventilation, anesthesia machines do not deliver ventilation modes and flow capabilities commonly used outside the operating room (OR). A paucity of published information exists to describe the operation of anesthesia machines, their technological and practical limitations, and special considerations to prevent harm when re-purposed. We provide technical information and practical guidance for the safe use of anesthesia machines in critically ill patients outside the OR.