Zonisamide is a novel anticonvulsant that is structurally and mechanistically unique, compared with other antiepilepsy drugs. Available in Japan and South Korea since 1989, it was approved in the United States in the year 2000 as adjunctive therapy for partial seizures in adults. There has been extensive clinical trial and clinical practice experience with zonisamide therapy in Japanese children. Open-label data from pediatric clinical trials conducted in Japan suggest that zonisamide is well tolerated and effective against partial- and generalized-onset seizures in children. Despite this wealth of open-label data, no formal pharmacokinetic studies and only one well-controlled trial of zonisamide's efficacy and safety in Japanese children have been completed to date. No controlled clinical trials of zonisamide in children have been completed in the United States or Europe. Additional controlled trials in children with partial- or generalized-onset seizures, infantile spasms, and Lennox-Gastaut syndrome are warranted to further delineate zonisamide's broad spectrum of efficacy and tolerability in children.