Posttraumatic stress disorder (PTSD) can develop following exposure to traumatic event(s) and is characterized by difficulties with intrusive thoughts, avoidance, hypervigilance, and negative alterations in mood and cognition. PTSD often co-occurs with substance-related and addictive disorders (SRAD), and this comorbidity of PTSD and SRAD is associated with a more severe clinical profile than either disorder alone. One of the reasons PTSD and SRAD are so commonly co-occurring is that they share underlying features such as difficulties with emotion regulation and emotional and behavioral avoidance. For many, substance use, gambling, and problematic gaming behaviors may serve as an avoidance strategy to manage PTSD symptoms. As such, PTSD interventions have been found to also alleviate SRAD symptoms. Several interventions have garnered strong empirical support in treating PTSD alone and PTSD+SRAD. This chapter aims to (1) provide background on the prevalence of PTSD+SRAD and shared mechanisms underlying these disorders, (2) review empirically supported treatments for PTSD and PTSD+SRAD, and (3) discuss clinical considerations for providers working with this comorbidity. Interventions reviewed in this chapter include evidence-based trauma-focused cognitive behavioral therapies including prolonged exposure, cognitive processing therapy, written exposure therapy, concurrent treatment of PTSD and substance use disorders using prolonged exposure, as well as pharmacological interventions. We also review support for these interventions in addressing complex and racial trauma. Treatment considerations for PTSD+SRAD will be discussed including rapport-building, diagnostic and symptom monitoring tools, and establishing safety.