Neonates undergoing surgery are at higher risk than older children for anesthesia-related adverse events. During the perioperative period, the maintenance of optimal hemodynamics in these patients is challenging and requires a thorough understanding of neonatal physiology and pharmacology. Data from animals and human cohort studies have shown relation of the currently used anesthetics may associate with neurotoxic brain injury that lead to later neurodevelopmental impairment in the developing brain. In this review, the unique neonatal physiologic and pharmacologic features and anesthesia-related neurotoxicity will be discussed.