Professional burnout is an evolving threat to workforce well-being, health care costs, and patient safety. Leaders of the National Academy of Medicine, Association of American Medical Colleges, and Accreditation Council for Graduate Medical Education recently established a collaborative to promote clinician well-being and resilience. This systematic review explored the relationships between clinician burnout, clinician engagement, organizational safety culture, and patient outcomes. Burnout was consistently associated with self-reported errors. However, when researchers assessed errors objectively, burnout did not reflect an increase in error rates. Few studies have addressed the relationship between burnout and staff engagement or safety culture. An Annual Perspective further explores how to address and prevent health care worker burnout.