Ondansetron is the first selective antagonist of the 5-hydroxytryptamine receptors (type 3) marketed for the prevention of emesis induced by antineoplastic agents. Ondansetron has been shown to be more active and less toxic than high-dose metoclopramide in patients submitted to cisplatin chemotherapy. Furthermore, when dexamethasone was added to ondansetron, its antiemetic efficacy increased significantly. In the prevention of emesis induced by a high single dose of cisplatin or by repeated low doses, ondansetron combined with dexamethasone has been shown to be the more efficacious and less toxic antiemetic treatment. However, in the prevention of delayed emesis from cisplatin, its role is still to be defined. In patients submitted to moderately emetogenic chemotherapeutic agents, ondansetron has shown an efficacy superior or equal to standard doses of metoclopramide, but is less toxic. Moreover, when compared with dexamethasone, its antiemetic efficacy and tolerability is similar; in this group of patients ondansetron should be used only when steroids fail. Ondansetron toxicity is generally mild; in particular, it does not induce extrapyramidal reactions. The most frequent side-effects are headache and constipation.