Carbamazepine and phenytoin are considered first-line therapies for children with partial seizures on the basis of the adult Veterans Administration studies, open-label controlled and uncontrolled pediatric studies, and clinical experience. Although many new antiepileptic drugs (AEDs) have demonstrated efficacy in controlled trials in adults with partial seizures, additional issues must be examined before these new AEDs are considered as first-line therapy for children with partial seizures. This article proposes three criteria for assessing the suitability of a new AED as first-line therapy for pediatric partial seizures: (a) demonstrated efficacy against pediatric partial seizures in two or more randomized, double-blind controlled trials involving patients less than 12 years old (with at least one of the trials utilizing a monotherapy design); (b) a favorable safety profile in monotherapy trials and no severe idiosyncratic reactions; and (c) ease of use in children across a wide range of ages. On the basis of these criteria, two new AEDs, oxcarbazepine (OXC) and topiramate (TPM), are suitable for consideration. OXC has demonstrated efficacy in monotherapy and adjunctive therapy in pediatric partial seizures, along with good tolerability and the ability to be titrated rapidly. TPM has also demonstrated efficacy and tolerability in pediatric partial seizures but should be titrated slowly. In addition, gabapentin (GBP) can be considered as first-line therapy for pediatric partial seizures if the preliminary analysis of a monotherapy trial is confirmed. There are not yet enough data on efficacy to support consideration of lamotrigine, tiagabine, felbamate, levetiracetam, or zonisamide as first-line therapy for pediatric partial seizures.