Computational modeling has become an increasingly useful tool for studying complex neuronal circuits such as the dentate gyrus. In order to effectively apply computational techniques and theories to answer pressing biological questions, however, it is necessary to develop detailed, data-driven models. Development of such models is a complicated process, akin to putting together a jigsaw puzzle with the pieces being such things as cell types, cell numbers, and specific connectivity. This chapter provides a walkthrough for the development of a very large-scale, biophysically realistic model of the dentate gyrus. Subsequently, it demonstrates the utility of a modeling approach in asking and answering questions about both healthy and pathological states involving the modeled brain region. Finally, this chapter discusses some predictions that come directly from the model that can be tested in future experimental approaches.