The efficacy of type 3 serotonin (5-hydroxytryptamin) (5-HT3) receptor antagonists in preventing nausea and vomiting associated with cancer chemotherapy, radiation therapy, and surgery and the role of practice guidelines for the use of these agents in controlling antiemetic drug costs without compromising patient care are described. Nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery can have a negative impact on quality of life and patient outcomes. The 5-HT3 receptor antagonists are effective for preventing nausea and vomiting from these causes. Oral 5-HT3 receptor antagonist therapy is as effective as intravenous therapy, while usually costing less. Various factors associated wtih the patient and the chemotherapy, radiation therapy, or surgery that increase the risk for nausea and vomiting have been identified. Practice guidelines have been developed in which 5-HT3 receptor antagonist therapy is reserved for patients at high risk for nausea and vomiting based on these various factors. The use of such practice guidelines at Memorial Sloan-Kettering Cancer Center limited antiemetic drug expenditures despite an increase in the number of patients receiving cancer treatment without compromising emetic control or quality of life. The use of special order forms improved compliance with the practice guidelines.