Not all patients respond to effective and approved treatment interventions, and there has been growing recognition in the medical field of these “resistant” or refractory illnesses (eg, treatment-resistant depression, resistant hypertension). In the field of substance use disorders, there has not been an explicit acknowledgement of treatment-refractory addiction (TRA) despite substantial evidence that many patients do not respond to standard-of-care treatment interventions. This article provides a justification for TRA as a critically important condition to recognize and define. TRA is not conceptualized as a diagnosis, but as a signal that a current treatment approach has not worked. The article addresses areas in need of research and consensus in order to ensure the approach to TRA is uniform, thoughtfully addressed, and data-driven. By explicitly acknowledging TRA, clinicians, researchers, and patients and their families can begin to explore the unique features of this population an...