Ondansetron is a potent and highly selective serotonin 5-HT3-receptor antagonist which has demonstrated important antiemetic activity and good tolerability in the prevention of chemotherapy-induced nausea and vomiting. Ondansetron is completely and rapidly absorbed from the gastrointestinal tract after oral administration, and does not accumulate with repeated oral administration. Owing to hepatic first-pass metabolism, its bioavailability is only about 60% compared with ondansetron administered by infusion over 15 minutes. Bioavailability is slightly increased when administered after a standard meal, and is not influenced by coadministration of antacids; a slightly enhanced bioavailability has been observed in patients with cancer. Since the time to reach peak concentration is 0.5 to 2 hours after oral ingestion, the drug should be administered at least 30 minutes before chemotherapy. Possible alternative ways of administration of ondansetron include intramuscular, subcutaneous and rectal administration, and oral controlled-release formulations. Ondansetron is widely distributed (volume of distribution approximately 160L) and binds moderately (70 to 76%) to plasma proteins; the elimination half-life averages approximately 3.8 +/- 1 hours. Clearance occurs by hepatic metabolism (95%) rather than renal excretion. Metabolites do not play a role in the activity of the drug, and there is no evidence of genetic polymorphic metabolism. Although aging is associated with decreased clearance and increased bioavailability, dosage adjustments are not required for the elderly, and may be necessary only in patients with severe hepatic impairment. Chemotherapeutic agents do not seem to modify the pharmacokinetics of ondansetron. There remains the question of whether control of emesis is related to systemic availability of ondansetron and, in consequence, the optimal dose and schedule of ondansetron is still to be identified with certainty.