Opioid use disorder and anxiety disorders co-occur at strikingly high rates, and this comorbidity is marked by a more severe clinical presentation and poorer prognosis for treatment. Given the substantial morbidity and mortality associated with these two disorders, it is imperative to understand factors related to the high rates of co-occurrence in order to inform the development of specialized treatments for this population. Several lines of study suggest that simultaneously addressing opioid-related and anxiety-related symptoms and processes, particularly intolerance of distress and pain-related anxiety, may yield improved outcomes for this high risk, vulnerable population. Future work is needed to identify other novel mechanisms as well as develop specialized treatments to augment standard medication-assisted treatment.