The identification and development of new agents and innovative treatment approaches remain a priority. The prognosis for patients with recurrent or metastatic head and neck cancer remains poor; thus participation in trials of promising investigational agents is an important option for these individuals. For patients with locally advanced tumors, combined modality treatment is undergoing rapid evolution. The optimal combination and sequence of therapies have yet to be determined. However, available data support an increasing role for chemotherapy especially as part of strategies to preserve organ function and treat unresectable disease.