Epigenetics refers to those mechanisms that allow a transient stimulus to induce long-lived programs of gene expression changes without altering the underlying DNA sequence itself. Epigenetic regulators function by catalyzing the modification of DNA or histone protein tails, which, in turn, up- or down-regulate the transcription of target genes. Originally thought to be static in terminally differentiated cells, it is now known that epigenetic processes are active and dynamic in mature neurons. Their function or perturbation may be sufficient to develop common neurological disorders such as epilepsy. This chapter provides a critical overview of key epigenetic changes detected in human patients and experimental epilepsy models. The chapter reflects on how these data impact epileptogenesis, what role epigenetic mechanisms may play in facilitating disease pathogenesis, and how it influences the chronic epileptic state. In the end, the chapter briefly discusses the potential for targeting epigenetic modulators as a new source of therapeutic intervention in epilepsy.