Inflammation in the central nervous system (CNS) is associated with epilepsy and is characterized by the increased levels of a complex set of soluble molecules and their receptors in epileptogenic foci with profound neuromodulatory effects. These molecules activate receptor-mediated pathways in glia and neurons that contribute to hyperexcitability in neural networks that underlie seizure generation. As a consequence, exciting new opportunities now exist for novel therapies targeting the various components of the immune system and the associated infl ammatory mediators, especially the IL-1β system. This review summarizes recent fi ndings that increased our understanding of the role of infl ammation in reducing seizure threshold, contributing to seizure generation, and participating in epileptogenesis. We will discuss preclinical studies supporting the hypothesis that pharmacological inhibition of specifi c proinfl ammatory signalings may be useful to treat drug-resistant seizures in human epilepsy, and possibly delay or arrest epileptogenesis.