Advanced squamous cell carcinoma of the head and neck (SCCHN) is both a local-regional and a systemic disease that is ineffectively managed by conventional surgery and radiotherapy. For patients with advanced but potentially curable (Mo) disease, the morbidity associated with conventional surgery or radiotherapy may be significant whereas the probability of lasting disease control is low. For those with recurrent or metastatic lesions, surgery or radiotherapy are rarely effective options. In this setting, chemotherapy has been evaluated as primary therapy for patients with recurrent or metastatic disease and as an adjunct to surgery or radiotherapy for those with potentially curable lesions. As palliative therapy, methotrexate remains the single agent of choice. Combination chemotherapy has been associated with a higher response rate but not improved survival when compared with methotrexate alone. Cisplatin, both as a single agent and in combination with 5-fluorouracil, is active against SCCHN, and may be superior to methotrexate in antitumor activity. The impact of induction and adjuvant chemotherapy or concurrent chemotherapy and radiotherapy in patients with potentially curable lesions remains controversial. A specific role for chemotherapy has not been confirmed by prospective randomized trial, but effective therapies have been achieved: Regimens with increased activity against squamous carcinomas have been reported, clinical trials with sufficient power to reach significant conclusions have been published, and organ preservation has been confirmed as an appropriate end point for studies of induction chemotherapy or concurrent chemotherapy and radiation. The clinical experience with chemotherapy for patients with recurrent or metastatic SCCHN as well as induction and adjuvant chemotherapy and concurrent chemotherapy and radiotherapy for those with potentially curable disease is reviewed, with particular emphasis given to trials involving cisplatin and to avenues for continued clinical investigation.