This article describes the historic experience of the development of antiemetic guidelines for patients taking chemotherapy drugs at Mayo Clinic Rochester. The initial guidelines for the use of serotonin (5-hydroxytryptamine3) receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting were developed in early 1995 and implemented in September 1995. In February 1997, the guidelines were reviewed and modified. In the spring of 1998, major changes were made based on new data from the literature and discussions with antiemetic authorities in the United States. These guidelines were implemented in July 1998. The guidelines were again reviewed and modified in December 1998. In addition, we compared costs associated with the 1997 guidelines and the December 1998 guidelines. The developed guidelines, utilizing clinically available agents, seem to provide high-quality patient care at a reasonable cost.