Abstract Purpose The use of buprenorphine, methadone, and long-acting naltrexone for treatment of opioid use disorder (OUD) is discussed, including a review of current literature detailing treatment approaches and action steps to optimize treatment in acute care and office-based settings. Summary The U.S. epidemic of opioid-related deaths has been driven by misuse of prescription opioids and, increasingly, illicit drugs such as heroin, fentanyl, and fentanyl analogs, necessitating a refocusing of treatment efforts on expanding access to life-saving, evidence-based OUD pharmacotherapy. Inpatient treatment of opioid withdrawal includes acute symptom control through a combination of nonopioid medications and long-term pharmacotherapy to lessen opioid craving and facilitate stabilization and recovery. Methadone and buprenorphine reduce opioid craving, increase treatment retention, reduce illicit opioid use, and increase overall survival. Buprenorphine has logistical advantages over methadone, such as greater flexibility of treatment setting and less risk of adverse effects. Studies have shown the efficacy of long-acting injectable naltrexone to be comparable to that of buprenorphine if patients are detoxified prior to initiation of therapy; however, patients with active OUD are often not able to complete the week-long period of opioid abstinence needed prior to initiation of naltrexone injections. Although buprenorphine is preferred by many patients and can be prescribed in office-based settings, there remains a paucity of physicians certified to prescribe it. Conclusion Buprenorphine has become the medication of choice for many patients with OUD, but its use is limited by the low number of physicians certified to prescribe the agent. Other agents studied for treatment of OUD include methadone and naltrexone.