Epilepsy is a disorder of abnormal excitability and synchronicity of aggregates of neurons that lead to paroxysmal behavioral or perceptual change. Most antiepileptic drugs (AEDs) decrease membrane excitability or increase postsynaptic inhibition, and may alter synchronization of neuronal networks. The attributes of an AED that reduce the tendency toward seizures may cause disruption of normal cerebral processes. Previous clinical studies suggest wide inter-individual variability of the effects of such AEDs. The options for antiepileptic treatment have dramatically expanded in the past decade and now allow tailoring of intervention for optimal management of individual patients. Current strategies to improve epilepsy care should include systematic monitoring to identify adverse effects of AEDs, and future approaches may involve creative applications of neuroimaging and genetic technologies to match patient characteristics to AED attributes.