A major challenge in understanding the neurobiological basis of epilepsy stems from the fact that numerous molecular, cellular, synaptic and network properties undergo significant, simultaneous alterations during epileptogenesis. The close integration of experimental findings with large-scale, data-driven computational simulations of control and epileptic neuronal networks offers a powerful tool towards the identification of key circuit parameters that may be particularly effective in controlling epileptic circuit behavior. To this end, we have been developing realistic microcircuit-based network models of the control and injured hippocampus in order to investigate questions related to normal hippocampal microcircuit function and the mechanistic bases of epilepsy. We will discuss the conceptual framework and biological basis of model development and show specific applications, including computational and experimental results concerning model validation, cell type specific hippocampal chronocircuit properties and the role of hub neurons in seizures. The talk will highlight the predictive and analytic power of freely shared, highly realistic, large-scale computational models in understanding normal circuit function and temporal lobe epilepsy.