The first edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in 1952. This publication was the first formal attempt to provide a nosology to guide the diagnosis of mental disorders, including substance use disorders (SUD). There have been four iterations of the nosology since 1952, and the sequential publication of each new edition has provided the foundation for a more enlightened perspective on diagnosing the range of psychiatric conditions. This article reviews the literature specific to the past revisions of the DSM up to and including the proposed changes on substance abuse/use for the DSM-5, the significance of substance use pathology, associated behaviors, as well as the social and political influences that impact substance use. Nosological changes will be reviewed as they relate to shifts in the conceptualization of substance-related diagnosis.