The authors of this editorial propose a five-step strategy for patient safety and quality improvement staff to leverage their skills to support patients, staff, and organizations during the COVID-19 pandemic. It includes (1) strengthening the system and environment, (2) supporting patient, family and community engagement and empowerment, (3) improving clinical care through separation of workflows and development of clinical decision support, (4) reducing harm by proactively managing risk for patients with and without COVID-19, and (5) enhancing and expanding the learning system to develop resilience.