Serotonin is a neurotransmitter involved in chemotherapy-induced emesis and ondansetron is a new drug endowed with selective antagonism against the 5HT3 receptors. Phase I-II studies have demonstrated its activity against acute emesis after single-dose cisplatin, reporting particularly low toxicity; in comparative studies with high-dose metoclopramide, it has been proved to be more effective and completely devoid of extrapyramidal side effects. Ondansetron has shown its activity and safety also in multiple-day cisplatin regimens. Its antiemetic efficacy is improved by the addition of dexamethasone. Preliminary data suggest its role also when used in single-dose administration. Its activity in the delayed phase of cisplatin emesis needs to be further explored.