Epilepsy is defined by the presence of recurrent, spontaneous seizures that involve brain-wide networks. Brain activity outside of seizures (interictal activity) is also often abnormal in epilepsy, but the relationship between these two phenomena is not well understood. In this chapter, we describe a method for imaging brain activity across the surface of the dorsal cortex in mouse models of epilepsy using Ca++ indicators, as well as how to analyze this activity to study both spontaneous seizures and interictal activity. The data generated from this approach can be used to (1) identify cortical areas that are susceptible to seizures and abnormal activity patterns, (2) investigate spontaneous seizure initiation, spread, and termination, (3) relate features of interictal abnormalities to seizures, and (4) evaluate the efficacy of therapies in normalizing cortical activity. The low cost, usefulness, and flexibility of the approach should encourage those investigating animal models of epilepsy and other neurological diseases to adopt it as part of their phenotyping repertoire.