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Ondansetron is a potent, highly selective 5HT3 receptor antagonist. Its exact mechanism in controlling nausea and vomiting is not fully understood. Chemotherapy and radiotherapy can trigger the release of 5HT in the small intestine, which initiates a vomiting reflex by activating vagal afferents through 5HT3 receptors. Ondansetron blocks this reflex. Additionally, activation of vagal afferents can release 5HT in the area postrema on the floor of the fourth ventricle, promoting emesis via a central mechanism. Therefore, ondansetron likely manages nausea and vomiting induced by chemotherapy and radiotherapy by antagonizing 5HT3 receptors in both the peripheral and central nervous systems. While the mechanisms for postoperative nausea and vomiting are not entirely known, they may share pathways with those of cytotoxic-induced nausea and vomiting.