The use of concurrent chemotherapy and radiation, or chemoradiation, has become the focus of increasing interest in the management of patients with squamous-cell head and neck cancer. Randomized trials comparing radiation therapy alone with radiation and single chemotherapeutic agents given concurrently have suggested benefit for several different drugs. Randomized multiagent chemoradiotherapeutic trials have been approached somewhat more tentatively in view of the anticipated additional toxicity. Nonetheless, several studies have been reported, and a more consistent survival benefit with chemoradiotherapy has been observed. Treatment regimens using rapidly alternating chemotherapy and radiation schedules have also resulted in an improvement in survival. Although these kinds of aggressive treatment approaches produce significant incidences of morbidity and may not be appropriate for all patients, a role for chemoradiotherapy in the definitive management of this disease is being defined.