Purpose of Review: This paper provides a narrative review of the co-use of alcohol and opioids, and its impact on biological, neurocognitive, and behavioral systems. In addition, data addressing co-use among patients receiving opioid-replacement therapy and those who have chronic pain are discussed. Recent Findings: Alcohol and opioids are among the most commonly used substances, and co-use has contributed to a growing number of accidental poisonings, emergency room visits, and overdose deaths. Prevalence of co-use is high among multiple populations, and severely impacts treatment outcomes. Summary: Substance abuse treatment for those that co-use alcohol and opioids is inadequate. Future research should further investigate salient influences on co-use and successful areas for intervention to address this treatment need.