Context: Seizure is a transient neurologic dysfunction caused by sudden abnormal firing of cerebral neurons. Epileptic syndrome is a complex of symptoms and signs that is characterized by not only the etiology but also the age at onset, seizure type, pattern of electroencephalography and prognosis. Evidence Acquisition: Treatment of the first seizures depends on their nature; some of them need no antiepileptic drugs (AED) therapy whereas the others should be treated appropriately. AEDs have long-and short-term adverse effects, interaction with other medications, and occupational and/or psychological consequences. Therefore, discontinuation of AEDs should be considered after a free-seizure period. Results: Studies show that the rate of seizure recurrence after AEDs withdrawal is about two to three times more than those who continue therapy; thus, the most difficult decision facing a neurologist is when to start medication and when/how it should be discontinued. Conclusions: This review explores the literature to answer above questions.