There is a significant need for advanced understanding of treatment of co-occurring posttraumatic stress disorder (PTSD) and substance use disorders (SUD). Approximately half of individuals seeking SUD treatment meet criteria for current PTSD, and individuals with co-occurring PTSD-SUD tend to have poorer treatment outcomes compared with those without such comorbidity. However, there is not sufficient empirical evidence to determine a best course of treatment for these individuals. This paper provides a review of the literature relevant to the treatment of co-occurring PTSD-SUD. To date, treatment studies have focused primarily on non-exposure-based psychosocial treatments, exposure-based psychosocial treatments, and medication trials. The most promising outcome data thus far are for psychosocial treatments that incorporate an exposure therapy component; however, further research is needed, particularly as related to how best to implement these approaches in real-world treatment settings.