Monotherapy remains the mainstay for treatment of epilepsy. On average, approximately 70% of patients with newly diagnosed epilepsy have seizures effectively controlled with one appropriately selected antiepileptic drug (AED). Moreover a significant proportion up to 50% of patients whose seizures are not effectively controlled by the initial AED treatment can be successfully managed by an alternative AED. The main benefits of monotherapy are less frequency of adverse effects, easier dosage, better compliance and less cost of treatment. Monotherapy with classic AED is efficacious but new AED occur to be equally effective and are better tolerated. The very serious adverse events as impairment of concentration and attention, polycystic ovary syndrome, hormonal disturbances are not reported with new AED. They have also very small number of pharmacokinetic interactions with other AED. Beside refractory epilepsy new AED should be considered for treatment of new diagnosed epilepsy especially for children, elderly patients, woman in reproductive age etc.