There is growing concern worldwide about the extent of psychoactive substance abuse and dependence disorders. Epidemiological data are needed to assess the prevalence and severity of the problem. Collecting this type of data is possible with a highly structured and reliable diagnostic interview. The problems involved in developing such an interview are discussed in this chapter. They include the absence of a unified concept of psychoactive substance dependence and a lack of a standardized system of diagnostic criteria. Recently a new instrument has been designed to assess psychoactive substance abuse and dependence disorders according to multiple diagnostic systems. The WHO/ADAMHA Composite International Diagnostic Interview Substance Abuse Module (CIDI-SAM) has been found to have excellent diagnostic reliability in a test-retest pilot study. This chapter describes the development and evolution of the interview and offers guidelines for operationalization of substance abuse and dependence criteria.