The goals of medicine tend to be framed around addressing suffering, pathology, and functional deficits. While this is a natural orientation when dealing with serious illness, it is also incomplete and neglects significant opportunities to improve the quality of life of patients, families, and clinicians. The “total enjoyment of life” is a multidimensional framework that can serve as a positive counterbalance to the “total pain of illness.” It allows clinicians, researchers, policymakers, and other stakeholders to take a systematic and comprehensive approach to the active promotion of well-being. The five opportunities for enhancing well-being in this framework are meaning, social connections, happiness/contentment, spiritual transcendence, and pleasure. Applying these concepts in clinical settings, patients, families, and clinicians can together find opportunities to increase the total enjoyment of life in the face of incurable and intractable illnesses. For family care partners, these concepts can be applied to improve self-care, enhance relationships, and develop more creative approaches to supporting a loved one living with illness. Clinicians working with these concepts may find their clinical work more satisfying and impactful and can also apply these concepts to their own lives to increase wellness. In clinical research, this framework can be applied to improve intervention effectiveness and relevance of outcome measures. Lastly, these concepts have the potential to impact public health approaches that focus on well-being and flourishing as the goal and metric of a healthy society.