While seizures ultimately result from aberrant firing of neuronal networks, several laboratories have embraced a non-neurocentric view of epilepsy to show that other cells in the brain also bear an etiologic impact in epilepsy. Astrocytes and brain endothelial cells are examples of controllers of neuronal homeostasis; failure of proper function of either cell type has been shown to have profound consequences on neurophysiology. Recently, an even more holistic view of the cellular and molecular mechanisms of epilepsy has emerged to include white blood cells, immunological synapses, the extracellular matrix and the neurovascular unit. This review will briefly summarize these findings and propose mechanisms and targets for future research efforts on non-neuronal features of neurological disorders including epilepsy.