The use of antiepileptic drugs in the treatment of epilepsy in children and adolescents, and first of all decision making on pharmacotherapy, may be demanding and complex given the various pharmacologic possibilities. Antiepileptic drugs should be prescribed according to the generic term of a single drug rather than the pharmaceutical/factory-protected name. Treatment of epilepsy should start with the first choice drug: the original or generic drug. Guidelines for pharmacotherapy of epilepsy in children are presented as the general principles of pharmacological treatment of epilepsy and as decision making about pharmacological treatment of epilepsy and epileptic syndromes in the Republic of Croatia. The paper also briefly reviews the most commonly used and most important antiepileptic drugs, their adverse effects and interactions. New antiepileptic drugs that are not yet on the primary or supplemental list of medicines in Croatia are also listed, but are applied in the treatment of epilepsy in children and are effective. The first choices for seizures with focal onset and focal epilepsy are oxcarbazepine (evidence level: class 1A (AAN) and GRADE 1B) and carbamazepine (evidence level: class 1A (AAN) and GRADE 1B). Antiepileptic drug of the first choice for seizures with generalized onset /generalized epilepsy in male patients is valproate (evidence level: class 1A (AAN) and GRADE 1A). Levetiracetam (evidence level: class 1B (AAN) and GRADE 1C) and etosuximid (the latter for absence seizures) (evidence level: class 1A (AAN) and GRADE 1B) are recommended as the drugs of the first choice in the treatment of generalized seizures/epilepsy in female patients since infancy due to possible teratogenic and other adverse effects on postnatal development after intrauterine exposure to valproic acid and valproic acid related drugs. It is certainly justified to use valproate in girls as a therapy in the case of inefficiency/antiepileptic side effects of the first choice therapy for generalized epilepsy, and when pregnancy is unlikely due to the severity of the disease itself.