The agonist substitution strategy, starting with methadone maintenance treatment discovered in the 1960s, has been a major advance in pharmacotherapy for opioid use disorder, converting an often refractory, chronic relapsing disorder with a high mortality rate into a disorder that is manageable. Multiple clinical trials and a meta-analysis have demonstrated the efficacy and effectiveness of mu-opioid partial agonist buprenorphine as a treatment for opioid use disorder. As a partial agonist with high receptor affinity, buprenorphine has a more favorable safety profile than methodone. Buprenorphine produces less opioid-like effects and tolerance than full agonists like methadone, and less opioid adverse effects including, importantly, less suppression of respiration. Buprenorphine is somewhat less effective than the full agonist methadone for treatment of opioid use disorder as evidenced by, for example, higher rates of dropout from treatment on buprenorphine. However, methadone maintenance is restricted to tightly regulated clinics, which are not acceptable to many patients and is not even available in many regions of the United States. In contrast, buprenorphine can be prescribed for treatment of opioid use disorder in the United States by any physician, nurse practitioner, or physician assistant, who has taken modest additional training. With the epidemic of opioid use disorder and overdose deaths expanding in the United States., expanding prescribing of buprenorphine is a critical component of the US response to the epidemic.