Addiction alone is challenging; when addiction co-occurs with another psychiatric disorder or chronic pain, its clinical course, diagnosis, and treatment become even more difficult as the two interact, synergize, and exacerbate each other. In 2013, the American Society of Addiction Medicine (ASAM) revised and expanded its criteria guide from the previous ASAM Patient Placement Criteria to ASAM Treatment Criteria for Addictive, Substance-Related, and Co-Occurring Conditions. The occurrence of substance use disorder (SUD) among schizophrenia patients is high—the lifetime rate was close to 50%. The odds of developing an alcohol use disorder were three times higher among schizophrenia patients compared to the general population and, for drug use disorder, the odds were six times higher. The chapter discusses some treatment strategies for helping individuals with co-occurring PTSD and addiction: Apply approaches that are exposure-based (past-focused treatments) and non-exposure-based (present-focused treatments). Prolonged exposure therapy (PE) is a highly effective and evidence-based treatment that has long been considered the gold standard for PTSD.