The lifespan risk of seizures is highest in the neonatal period. Current therapies have limited efficacy. Although the treatment of neonatal seizures has not changed significantly in the last several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. This article provides an overview of current approaches to the diagnosis and treatment of neonatal seizures, and some of the recent insights about the pathophysiology of neonatal seizures that may provide the foundation for better treatment are identified.