The etiology of chronic pain-related disability is not fully understood, particularly from a clinical perspective. Investigations to date have identified risk factors and elucidated some important processes driving the development of persistent pain problems. Yet this knowledge and its application are not always accessible to practicing physical therapists or other clinicians. This article aims to summarize the main psychological processes involved in the development of chronic pain disability and to derive some guidelines for treatment and future research. To this end, the focus is on the paradox of why coping strategies that are helpful in the short term continue to be used even when-ironically-they maintain the problem in the long term. To aid in summarizing current knowledge, 4 tenets that elucidate the etiology of chronic pain are described. These tenets emphasize that chronic pain disability is a developmental process over time, contextual factors set the stage for this development, underlying transdiagnostic psychological factors fuel this development, and the principles of learning steer the development of pain behaviors. With these tenets, an explanation of how a chronic problem develops for one person but not another is provided. Finally, hypotheses that can be empirically tested to guide clinical application as well as basic research are generated. In conclusion, understanding the psychological processes underlying the etiology of chronic pain provides testable ideas and a path forward for improving treatment interventions.