Through interdiction models, we infer the vulnerabilities inherent in an operational system. This chapter presents four applications of interdiction modeling: (a) to delay an adversary’s development of a first nuclear weapon; (b) to understand vulnerabilities in an electric power system; (c) to locate sensors in a municipal water network; and (d) to secure a border against a nuclear smuggler. In each case, we detail and interpret the mathematical model and characterize insights gained from solving instances of the model. We point to special structures that sometimes arise in interdiction models and the associated implications for analyses. From these examples, themes emerge on how one should model, and defend against, an intelligent adversary.