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Abstract This commentary highlights a research article published recently in Cell Stem Cell “Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy”. Generally, Lentini et al. reveal a strategy to fulfill in vivo glia-to-neuron reprogramming, which is a potential disease-modifying strategy for treatment of intractable seizures. Here, we describe exciting research advances in the treatment of intractable seizures based on this research article, summarizing its key findings, emphasizing its importance and providing further discussions. Further, issues worthy of further investigations are also postulated so that clinic translation can be better achieved.