Purpose of Review <p>Opioid use disorder (OUD) is a chronic condition with high relapse rates, posing significant public health challenges. This review examines the neurobiological mechanisms of relapse, risk factors, and the efficacy of current and emerging treatment strategies for OUD.</p> Recent Findings <p>Key neurobiological drivers of OUD include stress system dysregulation, dopamine deficits, and genetic predispositions, which contribute to addiction’s chronicity and relapse vulnerability. Medications like buprenorphine and methadone improve retention and reduce relapse but face barriers like stigma and limited access. Psychosocial interventions, including contingency management and mindfulness-based therapies, show promise when combined with medication-assisted treatment. Emerging therapies, such as neuromodulation, exercise, and psychedelics, target both neurobiological and behavioral components of OUD but require further validation.</p> Summary <p>Reducing OUD relapse demands an integrated approach, addressing accessibility barriers, enhancing treatment retention, and exploring innovative therapies. Expanding prevention strategies, such as genetic screening for at-risk populations, is crucial for improving outcomes and reducing the societal burden of OUD.</p>