Medically refractory neonatal seizures represent a major therapeutic challenge in neonatal intensive care units. Conventional antiepileptic drugs demonstrate limited efficacy. Previous studies documented a high frequency of off-label drug therapy in neonates. We sought to determine if pediatric neurologists are recommending treatment of neonatal seizures with newer agents, despite a lack of information about their safety or efficacy in this population. Surveys were distributed at the 2007 Annual Meeting of the Child Neurology Society. Responses from 55 pediatric neurologists were analyzed. Seventy-three percent (40/55) recommended treatment of neonatal seizures with one or both of levetiracetam and topiramate; 47% (26/55) recommended levetiracetam; and 55% (30/55) recommended topiramate. Despite an absence of data on neonatal pharmacokinetics of either drug, neurologists made different dosing recommendations for these two drugs (P = 0.003, chi-square test). Respondents considered both agents to be efficacious in the majority of cases; adverse effects were recognized more frequently with topiramate. These results highlight the urgent need for rigorous clinical trials to understand the risks and benefits of new drug therapies for neonatal seizures.