This article examines some basic principles of systems theory and applies them to the integration of psychobiology and behavior therapy in the evolution of behavioral medicine. Using the concepts of whole/part relationships, level and emergent property, and self-regulation and disregulation, it is proposed that all behavioral therapies involve psychobiological processes, and, therefore, indirectly impinge on physical health. It is argued that the distinction between behavior and biology is one of level, and, therefore, behavioral therapies are ultimately biobehavioral therapies having biobehavioral consequences. It is proposed that contrary to traditional reductionistic logic, modern advances in biology are providing strong justification for the importance of including psychological methods in treating diseases manifested at the biological level. Various clinical examples are used to demonstrate how systems theory can be applied to differential diagnosis and treatment, computing cost/benefit ratios of different treatments, and conducting comprehensive clinical research and evaluation. Assessing the interaction of biological, psychological, and social treatment modalities becomes the hallmark of responsible patient care. Implications of the systems conception of behavioral medicine for collaboration among health care providers, the training of future clinicians in different disciplines, and policy decisions regarding the larger social consequences of health care are considered.