The COVID-19 pandemic has suddenly challenged many healthcare systems. To respond to the crisis, these systems have had to reorganize instantly, with little time to reflect on the roles to assign to their patient safety (PS) and quality improvement (QI) experts. In many cases, staff who had a background in clinical care was called to support wards and critical care. Others were deemed “non-essential” and sent back to work from home, while their programmes were placed in hibernation mode. This has meant that many QI and PS experts with skills to offer in their field have ended up carrying out tasks unrelated to the current crisis. We believe that the skillset of patient safety and quality improvement personnel is essential for the successful implementation of the changes required to achieve the desired outcomes. An understanding of systems theory and the complexity of healthcare systems, human factors and reliability theories, and change methodologies is key to the success of any transformation programme. Here, we suggest a five-step strategy and actions through which PS and QI staff can meaningfully contribute during a pandemic by employing their core skills to support patients, staff and organizations: 1. Strengthen the system by assessing readiness, gathering evidence, setting up training, promoting staff safety and bolstering peer support. 2. Engage with citizens, patients and their families so that the solutions are jointly achieved and owned by both the healthcare providers and the people who receive care and in particular the citizens who are required to undertake preventive interventions. 3. Work to improve care, through actions such as the separation of flows, flash workshops on teamwork and the development of clinical decision support. 4. Reduce harm by proactively managing risk to both COVID-19 and non-COVID-19 patients. 5. Boost and expand the learning system, to capture improvement opportunities, adjust very rapidly and develop resilience. This is crucial as little is known about COVID-19 and its impacts on patients, staff and institutions.