Rural communities often have distinct contextual factors that impact residents' substance abuse behavior. However, most studies to date have focused either exclusively on urban populations or neglected to analyze data in a way that allows any rural/urban comparison. This is especially true for research examining nonmedical prescription drug use among adolescents. This article presents a review of the research on nonmedical prescription drug use focusing on rural residence as a risk factor for nonmedical use of pain relievers, stimulants, sedatives, and/or tranquilizers. While the research shows inconsistencies in rural/urban associations with adolescent nonmedical prescription drug use, some general conclusions are possible, which can be helpful in informing our prevention and intervention efforts. (Contains 1 footnote.)