Epilepsy has been considered mainly a neuronal disease, without much attention to non-neuronal cells. In recent years growing evidence suggest that astrocytes, microglia, blood leukocytes and blood-brain barrier breakdown are involved in the pathogenesis of epilepsy. In particular, leukocyte-endothelium interactions and eventually subsequent leukocyte recruitment in the brain parenchyma seem to represent key players in the epileptogenic cascade. Chemokines are chemotactic factors controlling leukocyte migration under physiological and pathological conditions. In the light of recent advances in our understanding of the role of inflammation mechanisms in the pathogenesis of epilepsy, pro-inflammatory chemokines may play a critical role in epileptogenesis.