Opioid use disorder is often a chronic, relapsing condition associated with increased morbidity and death; however, with appropriate treatment and follow-up, individuals can reach sustained long-term remission. This guideline strongly recommends opioid agonist treatment with buprenorphine-naloxone as the preferred first-line treatment when possible, because of buprenorphine's multiple advantages, which include a superior safety profile in terms of overdose risk. Withdrawal management alone is not recommended, because this approach has been associated with elevated risks (e.g., syringe sharing) and death from overdose in comparison to providing no treatment, and high rates of relapse when implemented without immediate transition to long-term evidence-based treatment. Here, Bruneau et al discuss management of opioid use disorders.