Seizures in the pediatric population commonly occur, and when proper rescue medication is not administered quickly, the risk of neurologic compromise emerges. For many years, rectal diazepam has been the standard of care, but recent interest in a more cost-effective, safe alternative has led to the investigation of intranasal midazolam for this indication. Although midazolam and diazepam are both members of the benzodiazepine class, the kinetic properties of these 2 anticonvulsants vary. This paper will review available data pertaining to the efficacy, safety, cost, and pharmacokinetics of intranasal midazolam versus rectal diazepam as treatment for acute seizures for children in the prehospital, home, and emergency department settings.