Patients continue to experience preventable harms. As a result, policy makers, physicians, and members of the public have intensified their efforts to improve patient safety. The Joint Commission publishes National Patient Safety Goals, the National Quality Forum recommends safe practices, the Centers for Medicare & Medicaid Services (CMS) will not pay for certain preventable complications, and health care organizations are taking action to reduce preventable harm. Although these actions are welcome, they raise ethical questions about selecting health care areas or patient populations for improvement efforts. In this Commentary, we explore the contentious issue of deciding what warrants a priority in patient safety and offer strategies to guide further discussion, policy, and research.