Purpose of Review <p>Opioid use disorder (OUD) is a chronic, relapsing illness associated with significant morbidity and mortality. Extended-release naltrexone (XR-NTX) is an evidence-based pharmacotherapeutic agent for the treatment of OUD. This review aims at reviewing the extant literature support XR-NTX, its limitations, and providing directions for future research.</p> Recent Findings <p>XR-NTX has been shown to be comparable to treatment with buprenorphine in head-to-head randomized controlled trials. XR-NTX has demonstrated clinical efficacy in several vulnerable populations with OUD including adolescents, criminal justice offenders, and patients infected with human immunodeficiency virus (HIV). XR-NTX has demonstrated efficacy for other substance use disorders including alcohol use disorder (AUD) and, when combined with bupropion, methamphetamine use disorder. Challenges to treatment include managing opioid withdrawal symptoms during XR-NTX induction as well relapse and overdose upon treatment discontinuation.</p> Summary <p>XR-NTX is a first-line pharmacotherapeutic option when treating opioid use disorder with demonstrated efficacy; challenges include supporting the patient during withdrawal to facilitate successful induction and encouraging compliance to mitigate risks of relapse and overdose.</p>