Chronic pain is a prevalent and costly issue for medicine and society. Although multiple interventions (eg, medication, surgery, regional anesthesia, and implantable devices) are available, symptoms often persist, with patients continuing to experience significant distress and disability. As a consequence, patients experience frustration, emotional distress, feelings of helplessness, and an overall sense of demoralization as they continue there quest to achieve relief. Psychological treatments are often considered when medical interventions prove to be inadequate but often are not integrated with traditional medical approaches. This article reviews biomedical, psychological, and biopsychosocial perspectives on persistent pain; outlines the contribution of cognitive, affective, and behavioral factors to the experience and response to chronic pain; describes a systematic approach to assessment that integrates physical and psychosocial contributions; and details a cognitive-behavioral perspective and approach to treatment that can serve as an important component, as well as providing guiding principles for comprehensive rehabilitation programs.