Despite the widespread and traditional use of polytherapy in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. Among other undesirable effects, it can produce subtle cognitive and behavioral changes and sometimes even exacerbate the epilepsy. Recent studies provide evidence that in many patients seizures can be controlled by carefully monitored monotherapy: Approximately 75% of newly diagnosed, previously untreated epileptic patients will enter a 2-year remission with this form of treatment. The theory has even been advanced that early control of seizures may help prevent the evolution of drug-resistant, chronic epilepsy. In some patients with chronic epilepsy, multiple-drug therapy can be reduced to single-drug treatment, usually with an improvement in cognitive function and without increase in seizures. Trials conducted to date have shown no evidence of superiority of any one major antiepileptic drug over another in control of a particular seizure type. The choice of antiepileptic drug for monotherapy may therefore be influenced by differences in toxic effects associated with individual agents. On the basis of clinical and psychometric evidence, carbamazepine has been shown to cause fewer adverse effects than other antiepileptic drugs on cognitive function, mood, and behavior.