The physical therapy profession has recently begun to address its role in preventing and managing opioid use disorder (OUD). This topic calls for discussion of the scope of physical therapy practice, and the profession's role, in the prevention and treatment of complex chronic illnesses, such as OUD. OUD is not just an individual-level problem. Abundant scientific literature indicates OUD is a problem that warrants interventions at the societal level. This upstream orientation is supported in the American Physical Therapy Association's vision statement compelling societal transformation and its mission of building communities. Applying a population health framework to these efforts may provide physical therapists with a useful viewpoint that can inform clinical practice and research, as well as develop new cross-disciplinary partnerships. This Perspective discusses the intersection of OUD and persistent pain using the disease prevention model. Primordial, primary, secondary, and tertiary preventive strategies are defined and discussed. This Perspective then explains the potential contributions of this model to current practices in physical therapy, as well as provide actionable suggestions for physical therapists to help develop and implement upstream interventions that may reduce the impact of OUD in their communities.