Cancer of the head and neck is an important medical problem, with approximately 46,500 cases predicted in the United States alone in 2003. Worldwide, more than 600,000 cases are anticipated. While several different histologic subtypes of head and neck cancer are seen in different parts of the world, more than 90% of tumors diagnosed in the United States are squamous cell carcinomas. Major strides in the management of this disease have been made in the last decade. These include, but are not limited to, the evolution of organ preservation, the increasingly well recognized role of concurrent chemoradiation therapy as either definitive therapy for unresectable disease or adjuvant therapy for high-risk surgical disease, and significant improvements in cytotoxic chemotherapy. The role of chemotherapy in this disease has been a subject of debate. Chemotherapy is now routinely included in the multimodality treatment of unresectable disease of the oral pharynx, larynx, and oral cavity. There is now increasing evidence supporting the role of induction chemotherapy in head and neck cancer. As intensified chemotherapy and radiation therapy have improved local control, the increasing incidence of distant metastases has necessitated the need for enhanced systemic control. These approaches are the topics of extensive investigations.