Immediate management of seizures includes stabilization, identification of the cause and specific treatment, and if needed, administration of an antiepileptic drug (AED) to prevent seizure recurrence. AED therapy is divided into standard (traditional) and alternative therapies. Alternative therapies include vitamins or cofactors specific for certain inborn errors of metabolism. Part 1 of this two-part Pharmacology Review examines some basic neonatal seizure concepts and the standard therapies (phenobarbital, phenytoin, fosphenytoin, and benzodiazepines); Part 2 reveiws alternative therapies and when to stop treatment. Seizures represent the most specific indication of neonatal neurologic insults. (1)(2) The incidence of neonatal seizures ranges from 1 to 5:1,000 live births. (2) It is vital to recognize neonatal seizures, determine their cause, and treat them because if they continue, they could interfere with supportive functions, such as respirations and feeding, and cause brain damage. (1)(2) Although seizures in an older child may be idiopathic or genetic, most neonatal seizures have a specific cause. In the series by Mizrahi and Kellaway, (3) the most common cause was hypoxic-ischemic encephalopathy (32%), followed by intracranial hemorrhage (17%), central nervous system infection (14%), infarction (7%), metabolic abnormalities (6%), inborn errors of metabolism (3%), and unknown (10%). The clinical manifestations of seizures may differ in the neonate compared with the older child and may not be as obvious. Volpe classified neonatal seizures as subtle or fragmentary seizures (more common in the preterm infant), clonic (focal or multifocal), tonic (focal or generalized), and myoclonic (focal, multifocal, or generalized). (1)(2) The generalized tonic-clonic seizure is unusual in the newborn, but it may be seen in genetic epilepsies. Electroencephalography (EEG) may be useful for confirming neonatal seizures when they are suspected. However, not all seizures have an EEG correlate, which makes diagnosis difficult. Mizrahi and Kellaway categorized seizures as …