Abstract: Epilepsy is one of the most commonly seen neurological disorders. Acute seizures can be induced by many factors, such as loss of balance between excitatory/inhibitory system, neuroinflammation and degeneration of neurosystem. Currently, most of the traditional antiepileptic drugs functioning on ion channels are actually working to prevent seizures rather than cure epilepsy thoroughly. Based on a detail reviewing of the latest progress on epileptogenesis, we focus on the most promising directions of treatment targeting on the underlying mechanisms of disease modification and prevention, so as to embrace the coming new era of comprehensive treatment for epilepsy.