The overall survival of patients with advanced squamous cell carcinoma of the head and neck (SCCHN) has not changed despite recent advances in surgical and radiotherapeutic techniques. For most patients with advanced disease, the morbidity associated with conventional surgery or radiotherapy is unacceptably high while the probability of locoregional and distant control of disease is low. The use of chemotherapy with surgery or radiotherapy for patients with SCCHN remains a controversial but highly promising treatment that attempts to improve locoregional control and overall survival or facilitate reductions in the locoregional treatment required for control of disease. Since the early 1960s, numerous trials have evaluated the impact of induction and adjuvant chemotherapy or concurrent chemotherapy and radiotherapy in the management of patients with advanced, but potentially curable, (M0) lesions. While a specific role for chemotherapy in the treatment of patients with SCCHN has not been confirmed by prospective randomized trials, considerable progress in the development of effective therapies has been achieved recently. This progress is characterized by the definition of chemotherapy with increased activity against squamous cell carcinomas and the organization of clinical trials with sufficient power to reach significant conclusions. This article reviews the experience with induction and adjuvant chemotherapy and concurrent chemotherapy and radiotherapy in the multidisciplinary treatment of patients with advanced SCCHN. The potential advantages as well as clinical experience with chemotherapy in these settings are presented.