Epilepsy is a life-threatening chronic disease in a state of neuronal over electric activity. The precise nature of the seizure recurrence has not been clearly. Synapses can be divided into silent and functional synapse.Silent synapses, defined as structural specializations for neurotransmission that do not produce a physiological response in the receiving cell, may occur frequently in neural circuits. Models of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD) of glutamatergic synapses, are believed to underlie the seizure occurrence. Silent synapses containing only NMDA receptors are transformed within minutes into activated synapses postsynaptically AMPA receptor insertion and presynaptic transmitter releasing (BDNF-Cdc42 (brain derived neurotrophic factor-) signaling, Calcium influx,cAMP(Cyclic Adenosine monophosphate) signal pathway. All previous mentioned genes and proteins were abnormal in epilepsy patients and animal models. Future experimental and clinical studies are needed a better understanding on the mechanisms of silent synapses in epilepsy.