This review highlights the most important recent advances in the chemotherapeutic management of patients with squamous cell carcinoma of the head and neck. Previous chemotherapy trials must be interpreted with caution in the absence of information concerning important prognostic variables, such as prior treatment, nutritional and performance status, and the heterogeneity of primary sites. In patients who have recurrent or metastatic disease, methotrexate, platinum, and bleomycin are three active drugs when used as single agents. There is no evidence that high dose methotrexate therapy is superior to more conventional weekly intravenous administration of methotrexate in the treatment of recurrent disease. Platinum is a new agent that has demonstrated activity against hematogenous as well as regional disease. In the absence of evidence of a dose-response curve for platinum, the lower dosage schedules that can be used with acceptable toxicity on an outpatient basis should be selected. Combination chemotherapy has resulted in a high proportion of objective responders and approximately 20 per cent complete remissions with any of several platinum containing regimens. However, the median duration of response remains short, and none of the combination drug programs has as yet been established to be superior to single agent chemotherapy in a randomized trial. Both single agent and combination chemotherapy programs have been used prior to initial surgery or radiation in patients with advanced inoperable but nonmetastatic disease. Despite dramatically higher response rates over those obtained with the same drugs used in recurrent disease, there is as yet no evidence that chemotherapy given in this manner has resulted in improved disease free or overall survival compared with local treatment alone. Similarly, the use of adjuvant chemotherapy following tumor clearance to eradicate potential micrometastatic disease is currently under investigation and cannot be recommended in the absence of a controlled trial. This article reviews the clinical trials currently in progress both for patients with recurrent squamous cell carcinoma of the head and neck and those with advanced local or regional disease.