Physician professionalism is influenced by both environmental and personal factors, one of which is physician well-being. Yet, a variety of stressors inherent in medical training and practice can erode a physician's sense of well-being and contribute to distress. This article reviews the epidemiology of physician distress; describes what is known about the relationships between distress, well-being, and professionalism; and discusses personal and environmental factors that contribute to professionalism among physicians.