Despite the substantial interest and investment in research on breast cancer screening, there is uncertainty about the magnitude of mammography’s benefits and harms and how to select patients and screening strategies to optimize the balance between benefits and harms. In the face of such uncertainty, thoughtful, evidence-based guidelines can play a powerful role in shaping policy and practice, supporting decision making by clinicians and patients, and identifying key research priorities. In this issue of JAMA, Oeffinger et al1 present updated breast cancer screening recommendations from the American Cancer Society (ACS), an influential voice in cancer policy and clinical care in the United States for more than 100 years.2