It is now clearly established that microglia and astrocytes become reactive in brain regions experiencing seizures both in human and experimental epilepsies. The expression of these reactive phenotypes lead to the dysregulation of the physiological functions normally fulfilled by these glial cells and to the acquisition of inflammatory properties through which they influence the activity and the fate of brain cells, including neurons, glia and cells of the blood vessels. In this chapter, we review how dysregulation of astrocyte and microglia physiological functions and the emergence of specific reactive states impact epilepsy progression.