ABSTRACT: The dramatic increase in opioid misuse, opioid use disorder (OUD), and opioid-related overdose deaths in the United States has led to public outcry, policy statements, and funding initiatives. Meanwhile, alcohol misuse and alcohol use disorder (AUD) are a highly prevalent public health problem associated with considerable individual and societal costs. This study provides a critical review of alcohol and opioid misuse, including issues of prevalence, morbidity, and societal costs. We also review research on interactions between alcohol and opioid use, the influence of opioids and alcohol on AUD and OUD treatment outcomes, respectively, the role of pain in the co-use of alcohol and opioids, and treatment of comorbid OUD and AUD. Heavy drinking, opioid misuse, and chronic pain individually represent significant public health problems. Few studies have examined co-use of alcohol and opioids, but available data suggest that co-use is common and likely contributes to opioid overdose-related morbidity and mortality. Co-use of opioids and alcohol is related to worse outcomes in treatment for either substance. Finally, chronic pain frequently co-occurs with use (and co-use) of alcohol and opioids. Opioid use and alcohol use are also likely to complicate the treatment of chronic pain. Research on the interactions between alcohol and opioids, as well as treatment of the comorbid disorders is lacking. Currently, most alcohol research excludes patients with OUD and there is lack of measurement in both AUD and OUD research in relation to pain-related functioning. Research in those with chronic pain often assesses opioid use, but rarely assesses alcohol use or AUD. New research to examine the nexus of alcohol, opioids, and pain, as well as their treatment, is critically needed.