Prescription medicine misuse is a growing problem in college campuses across the US. The Center for Disease Control (CDC) recently declared that the problem has reached epidemic proportions and is leading to a significant loss of lives every day. Norms-based public health campaigns that have been used in the past to address substance abuse issues among college students have had mixed success rates. Using the theory of normative social behavior, this study argues that a lack of focus on relevant mediators and moderators could be responsible for the failure of previous norms-based campaigns. Specifically, we test and support the mediating influence of perceived outcome expectations and injunctive norms on the effect of descriptive norms on intentions to misuse prescription medicines. In addition, perceived self-efficacy and trait reactance moderated the role of descriptive norms on outcome variables. Theoretical and practical implications of the findings are discussed.