AbstractChemotherapy has traditionally been relegated to a late palliative role in the management of head and neck cancer. For advanced disease in patients previously treated with surgery or radiation therapy, methotrexate, which has a response rate of approximately 50%, is the best single agent available. Other orally or systemically administered single agents–such as bleomycin, adriamycin, hydroxyurea, and cis‐platinum–produce responses less frequently than methotrexate. Intraarterial chemotherapy with single‐agent methotrexate or with combinations– including methotrexate, vinblastine sulfate (Velban), cyclophosphamide (Cytoxan), and 5‐fluorouracil (5FU)–can match the response rate of systemic methotrexate, but all require inpatient treatment and significant technical expertise. Programs utilizing chemotherapeutic combinations have not produced remission rates or durations of remission greater than those achieved with methotrexate alone. Chemotherapy has also been used in combination with other modalities. In two studies, chemotherapy combined with irradiation produced improvement in median or overall survival in comparison to irradiation alone. Many similar studies have been negative. Recent trials of chemotherapy used preoperatively in the treatment of head and neck cancer have not yielded decreased recurrence rates or increased overall survival rates in comparison to surgery alone, but they do appear to have prolonged the diseasefree interval following defin