The combination of PTSD and substance abuse is both common and problematic. In this chapter we review the following questions: 1) What is the relationship between PTSD, Alcoholism, and Drug Abuse? 2) Can the general "dual diagnosis" literature be of help? 3) Is the phenomenology of PTSD combined with alcoholism and/or drug abuse either unique or specific? 4) Does current pathophysiologic data allow conceptualization of a neurobiological model of PTSD, alcoholism, and drug abuse? 5) Drawing on these ideas, on the limited treatment literature, and the "dual diagnosis" literature, can we develop rational assessment and treatment approaches? Available literature suggests that diagnoses can be validly applied to these patients; that the illnesses must be treated simultaneously as co-primary illnesses; that extreme psychological symptoms reduce the efficacy of alcoholism or drug abuse treatment; and that effective control of these symptoms improves treatment outcome.