Opioid overdose deaths and opioid-related harms have reached unprecedented levels, particularly as compounds such as xylazine and fentanyl have infiltrated the drug supply. Harm reduction strategies are especially relevant in this climate, as they aim to reduce drug -related harms independently of whether an individual chooses to enter treatment or abstain from opioid use. Assessment of harm reduction strategies should consider targets beyond substance use. The purpose of this narrative review is to summarize existing harm reduction strategies in the United States and elsewhere and to describe how outcomes of these strategies could be assessed. Strategies designed to reduce opioid-related harms include syringe exchange programs, overdose education and naloxone distribution, supervised consumption sites, injectable opioid agonist treatment, safer supply programs, drug checking, and decriminalization. Outcomes besides abstinence that could be considered include reductions in substance use patterns that are associated with a high likelihood of negative consequences (e.g., solitary use and polydrug use), reductions in severity of opioid use disorder or early remission of opioid use disorder, improved quality of life and psychological health, improvements in community functioning including linkage and adherence to treatment, and reductions in the incidence of infectious disease. As opioid overdose deaths and related harms continue to rise, harm reduction strategies have become critically important. Harm reduction strategies for opioid use disorder should be considered in the context of outcomes that extend beyond measuring drug use, to capture benefits such as reduced mortality and greater well-being and quality of life.