Several of the newer antiepilepsy drugs have not been tested as monotherapy in controlled trials. Zonisamide is a broad-spectrum antiepilepsy drug indicated for the adjunctive treatment of partial seizures in adults. However, several small, open-label studies have indicated that it may be safe and effective as monotherapy. The present chart review study was conducted to evaluate the safety and effectiveness of zonisamide monotherapy in a pediatric and young adult patient group. Patient records at the Blue Bird Circle Clinic for Pediatric Neurology were reviewed to identify patients receiving zonisamide monotherapy. Efficacy was assessed from seizure diaries and patients' subjective evaluations. Safety and tolerability were evaluated by analysis of adverse events and change in body weight. The study included 131 patients aged 1 to 21.8 years with a broad spectrum of seizure types and epilepsy syndromes. A total of 101 patients (77.1%) achieved a 50% or greater decrease in seizure frequency, including 39 patients who achieved seizure freedom. Zonisamide monotherapy was well tolerated, with three patients (2.3%) discontinuing for adverse events. These results support open-label studies from Japan reporting that zonisamide monotherapy is safe and effective in pediatric and young adult patients.