Over the last decade, the Lucian Leape Institute has explored five key areas in health care to advance patient safety. These include medical education reform, care integration, patient and family engagement, transparency, and joy and meaning in work and workforce safety for health care professionals. This review highlights progress to date in each area and the challenges that remain to be addressed, including increasing clinician burnout and shortcomings of existing health information technology approaches. The authors also suggest opportunities for further research such as measuring the impact of residency training programs. In a past PSNet interview, Dr. Tejal Gandhi, president of the IHI/NPSF Lucian Leape Institute, discussed improving patient safety at a national level.