Abstract | Opioid use disorder (OUD) is a chronic relapsing disorder that, whilst initially driven by activation of brain reward neurocircuits, increasingly engages anti-reward neurocircuits that drive adverse emotional states and relapse. However, successful recovery is possible with appropriate treatment, although with a persisting propensity to relapse. The individual and public health burdens of OUD are immense; 26.8 million people were estimated to be living with OUD globally in 2016, with >100,000 opioid overdose deaths annually, including >47,000 in the USA in 2017. Well-conducted trials have demonstrated that long-term opioid agonist therapy with methadone and buprenorphine have great efficacy for OUD treatment and can save lives. New forms of the opioid receptor antagonist naltrexone are also being studied. Some frequently used approaches have less scientifically robust evidence but are nevertheless considered important, including community preventive strategies, harm reduction interventions to reduce adverse sequelae from ongoing use and mutual aid groups. Other commonly used approaches, such as detoxification alone, lack scientific evidence. Delivery of effective prevention and treatment responses is often complicated by coexisting comorbidities and inadequate support, as well as by conflicting public and political opinions. Science has a crucial role to play in informing public attitudes and developing fuller evidence to understand OUD and its associated harms, as well as in obtaining the evidence today that will improve the prevention and treatment interventions of tomorrow.