The management of chemotherapy-induced nausea and emesis presents a major problem in children with cancer. The anti-emetic properties of the 5-HT3 receptor antagonist ondansetron are well documented in adults receiving cytotoxic chemotherapy. Experience in the treatment of children is still limited. Here we present a review of the literature on the anti-emetic treatment with ondansetron in children. Moreover, we provide recommendations on the use of ondansetron during anti-neoplastic chemotherapy and radiotherapy in pediatric oncology.