There is a disproportionate focus on pain over pleasure in policy-relevant research on drugs. This is unfortunate because theories of and findings on drug-involved pleasure can be used to inform knowledge of drug-involved pain. The cross-fertilization of theories and findings is bolstered by the availability of a conceptual framework that links drug-involved pain and pleasure in a comprehensive, powerful, simple, and instrumental manner. This article proposes such a framework. It consists of four types of drug-involved pain and pleasure: drug-specific corporal, drug-related corporal, economic, and social. This quaternary scheme is illustrated with findings from four literatures, namely, those on methamphetamine use, alcohol-related sexual contact among college students, resource transfer among drug users and dealers, and relational and communal issues related to drugs. The article concludes with implications for the field.