This article describes advances in the behavioral self-management of chronic disease from the perspective of a 25-year trajectory of National Institute of Health-funded research in arthritis and cardiopulmonary diseases that has sought to develop a transdisciplinary understanding of how applied behavioral science can be used to improve health behaviors, functional status, and health outcomes. The article traces the arc of a novel research program--conducted in collaboration with physician-scientists at Columbia, Weill Cornell Medical College, and New York University School of Medicine--that runs through social cognitive theory, behavioral economics, and the emerging science of positive psychology in an effort to develop promising new approaches to fostering the adoption and maintenance of health-related behavioral change. The article concludes with what has been learned and what the implications of the work are for advancing behavioral self-management and patient education to improve patient outcomes and achieve the compression of morbidity. [The Elizabeth Fries Health Education Award Lecture on which this article is based was presented at the 68th Annual Meeting of the Society for Public Health Education (Denver, Colorado, March 31, 2017).]