None of the available antiemetics is entirely effective, perhaps because most of them act through the blockade of one receptor. There is a possibility that a combination of antiemetics with different sites of activity would be more effective than one drug alone for prophylaxis against postoperative nausea and vomiting (PONV).The clinical use of combined traditional antiemetics, including antihistamines (e.g. diphenhydramine), butyrophenones (e.g. droperidol) and benzamides (e.g. metoclopramide), for the prevention of PONV is limited because of the possibility of additive central nervous system toxicity, such as delayed emergence, drowsiness and extrapyramidal reactions. The efficacy of a combination of a serotonin 5-HT3 receptor antagonist (ondansetron, granisetron or tropisetron) and dexamethasone is superior to that of 5-HT3 receptor antagonists alone for the prevention of PONV, suggesting that dexamethasone enhances the antiemetic efficacy of 5-HT3 receptor antagonists. The combination of a 5-HT3 receptor antagonist with a traditional antiemetic (droperidol, metoclopramide or promethazine) acting at a different emetogenic receptor is more effective in reducing the incidence of PONV than each antiemetic alone acting at one receptor site. The risk of undesirable adverse effects does not increase with the combination of a 5-HT3 receptor antagonist and a traditional antiemetic at the doses commonly used for PONV, because of the absence of drug interactions. The combination of a 5-HT3 receptor antagonist (ondansetron) with other agents (propofol and CP-122721) reduces the incidence of PONV to a greater degree than monotherapy. However, no data are available for the combination of 5-HT3 receptor antagonists and small doses of propofol for the prevention of PONV.Further studies are needed to evaluate the efficacy and safety of combination antiemetic regimens for PONV. Knowledge regarding combinations of these antiemetic drugs may be necessary to completely prevent PONV.