Hepatic clearance of chemotherapy drugs is increased by many antiepilepsy drugs. At our institution, new-onset seizures in children on chemotherapy are treated with gabapentin, a nonhepatic enzyme inducer. The charts of all children given gabapentin for seizures were reviewed. At a median follow-up of 34 months, seizures were controlled in 74% of 50 children given gabapentin monotherapy as initial treatment: 91% of the leukemia group, 57% of the brain tumor group, and 75% of the other tumor group. Seizures were controlled in 49% of 59 children in whom gabapentin was added to other antiepilepsy drugs: 43% of the leukemia group, 53% of the brain tumor group, and 50% of the other tumor group. More than one seizure at presentation, focal neurologic deficits, high-dose methotrexate, brain irradiation, and T2-weighted signal abnormality around the brain tumor cavity predicted uncontrolled seizures. Only 8 children (7%) reported adverse effects, and the drug was discontinued in two. Gabapentin effectively controls seizures in children receiving chemotherapy and is well tolerated.