Mechanisms of epileptogenesis and drug resistance are still mysterious. Of recent clinical and experimental studies have shown that dysfunction of the blood-brain barrier (BBB) contributes to epileptogenesis and drug resistance. It is now recognized that cytokines exacerbate the excitability and permeability of the BBB, which was recently confirmed by studies showing that treatment of inflammation reduces epileptogenesis. Moreover, we have described an association between pathological angiogenesis and BBB permeability in the tissue of patients with excision of drug-resistant TLE. With experimental models, it was revealed an activation of the VEGF-VEGFR2 by seizures leading to rapid degradation of the BBB.