Postoperative nausea and vomiting (PONV) and pain are the most common complaints following anesthesia and surgery, and due to negative emotional impact on patients, they cause prolonged postoperative recovery. The incidence of PONV is 20-30% during the first 24h after anesthesia. Both peripheral and central mechanisms are involved in control of emesis. Factors Many factors associated with anesthesia and surgery may affect PONV: patient's age and sex, history of PONV after pervious anesthesia, administration of antiemetics prior to operation, type and duration of operation, type of premedication, induction agent, maintenance agent, reversal of muscle relaxation, treatment of postoperative pain and movement of patients. Antagonists of 5-hydroxytryptamine-3 (5-HT3) receptors Ondansetron is a competitive serotonin type 3 receptor antagonist important in prevention of PONV. However, if 5-HT 3 receptor antagonists are effective against nausea and vomiting after a variety of anesthetic and surgical procedures, then at last we may have the key to the mechanism of PONV. Prophylaxis with a combination of antiemetic drugs is more effective in prevention of PONV.