Survival rates for children with cancer have increased dramatically over the past few decades. Development of new chemotherapeutic agents and the expanded use of older agents have had a major impact on this celebrated improvement. Chemotherapy can have, however, significant toxicity on the nervous system. The most common neurologic complications involve acute alterations in consciousness, leukoencephalopathy, seizures, cerebral infarctions, paralysis, neuropathy, and ototoxicity. Most of the information on toxicity comes from prospective reports and the adult patient population. Methotrexate, cyclosporin, and platinum compounds are the most frequently cited. No prospective studies have been done to evaluate chemotherapy-induced neurotoxicity in the pediatric population, and the exact incidence of such complications is unknown. Such investigation is greatly needed, as it may lead to a better understanding of how chemotherapy affects the nervous system and ultimately help develop more strategies to prevent drug-related neurotoxicity in pediatric cancer patients.