Migraine, according to the criteria of the International Headache Society, occurs in about 5 to 10% of children and adolescents. Pediatric migraine can cause a significant impact on quality of life. As stated by the American Academy of Neurology and Child Neurology Society's migraine guidelines, situations for prophylaxis consideration include recurring migraines that significantly interfere with daily activities, despite acute therapy; frequent headaches; contraindication, overuse, or failure of acute therapy; adverse reactions to acute therapy; cost of acute and preventive therapies; patient preferences; and presence of uncommon migraine conditions. Preventive therapy may be warranted in as many as 30% of young patients with migraine seen in tertiary headache centers. Headache related disability can be measured by scoring systems such as the Pediatric Migraine Disability Assessment Scale. Numerous medications have been studied to prevent migraines in children, including antihistamines, antidepressants, and antihypertensive agents. However, few high quality clinical trials actually demonstrate efficacy in this population. Recently, many studies dealt with the use of antiepileptic drugs in this indication but there is a paucity of placebo controlled studies. Both topiramate (TPM) and divalproex sodium have been studied in a randomized-controlled study. Only TPM showed efficacy, though, clearly, further controlled trials are needed to confirm these data. Besides unproven efficacy, adverse effects of valproic acid, such as weight gain, somnolence, and alopecia may limit its use. Additional studies are warranted before recommending levetiracetam (LVT), zonisamide (ZNS) and gabapentin (GBP) agents for migraine prophylaxis in children and adolescents.