A n estimated 14 to 18 million Americans meet the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (4th ed., 1994) criteria for alcohol abuse or dependence (NIAA, 2004). In addition, there is a high rate of co-morbidity between substance abuse and mental illness (Greenfield & Hennessy, 2004). As a result, the assessment of substance use is essential in any clinical context (Adesso, Cisler, Larus, & Hayes, 2004). The use of patient self-reports in the assessment of substance abuse is supported by the literature (Babor, Brown, & Del Boca, 1990). That is, directly asking patients about their substance use is likely to provide more reliable information than indirect methods of questioning. However, in some settings and contexts, substanceabusing individuals might have incentives not to accurately report the extent and negative impact of their use. As a result, the use of multiscale inventories that can examine response style in the assessment of substance abuse is recommended (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). The objective of this chapter is to critically discuss the clinical application of the Personality Assessment Inventory (PAI; Morey, 1991) in substance abuse settings and to provide base rate data on PAI validity scales for two different types of substance abusing populations and settings.