The COVID-19 pandemic has presented novel challenges for the entire health-care continuum, requiring transformative changes to hospital and post-acute care, including clinical, administrative, and physical modifications to current standards of operations. Innovative use and adaptation of long-term acute care hospitals (LTACHs) can safely and effectively care for patients during the ongoing COVID-19 pandemic. A framework for the rapid changes, including increasing collaboration with external health-care organizations, creating new methods for enhanced communication, and modifying processes focused on patient safety and clinical outcomes, is described for a network of 94 LTACHs. When managed and modified correctly, LTACHs can play a vital role in managing the national health-care pandemic crisis.