There are unique stressors faced by health professionals that begin during the educational process and continue throughout training and into practice. While stress is expected owing to the intense nature of the work in health care, the systems in which faculty and health professionals work often intensifies this already stressful environment and can lead to negative mental and physical effects. In this National Academy of Medicine discussion paper, authors argue for a bold new strategy for tackling stress in the health professions. This strategy involves taking a multifaceted systems approach that includes everyone across the health professions, beginning in the learning environment, working together toward a common goal of promoting well-being. A systems-based approach acknowledges that stress, anxiety, and depression leading to burnout, suicide, or other unhealthy behaviors do not stem from a single source but rather are the culmination of multiple forces working against health.