The increasing prevalence of multimorbidity in the United States and the rest of the world poses problems for patients and for health care providers, care systems, and policy. After clarifying the difference between comorbidity and multimorbidity, this article describes the challenges that the prevalence of multimorbidity presents for well-being, prevention, and medical treatment. We submit that health psychology and behavioral medicine have an important role to play in meeting these challenges because of the holistic vision of health afforded by the foundational biopsychosocial model. Furthermore, opportunities abound for health psychology/behavioral medicine to study how biological, social and psychological factors influence multimorbidity. This article describes three major areas in which health psychologists can contribute to understanding and treatment of multimorbidity: (a) etiology; (b) prevention and self-management; and (c) clinical care. (PsycINFO Database Record (c) 2019 APA, all rights reserved).