The co-occurrence of post-traumatic stress disorder (PTSD) and substance use disorder (SUD) is well documented. The body of research regarding people with this comorbidity demonstrates that they often have more complex clinical presentations, face multiple or prolonged courses of treatment, and often suffer worse treatment outcomes than either condition alone. Moreover, due to this, there is often a clinician belief that SUD must be addressed prior to engagement in trauma-focused treatment despite increasing evidence to the contrary. The purpose of this chapter is to provide practical guidance on the implementation of cognitive processing therapy (CPT) to treat PTSD/SUD. This chapter first provides an overview of the comorbidity and clinical problems faced by individuals with co-occurring PTSD/SUD, as well as a review of the literature on the effectiveness of CPT in treating this comorbidity. We then present practical guidance for clinical applications of CPT in treating clients presenting with PTSD/SUD, including suggested techniques, language, and minor modifications to address comorbid SUD. In this section, we also present a case example to illustrate the clinical application through different stages of treatment. We conclude the chapter with a discussion of limitations in the existing research and future directions for CPT in treating PTSD/SUD.