Head and neck cancers account for less than 5% of all cancers and for less than 3% of all cancer deaths in the United States. The populations at risk for head and neck cancers are those who have a long-standing history of smoking and alcohol use. More recently, the incidence of oropharyngeal cancer in younger populations has been increasing and is associated with exposure to the human papillomavirus. This subset of patients appears to have a better overall prognosis and to respond better to treatment. This review is limited to head and neck cancers of squamous cell histology, which constitute more than 90% of head and neck cancers. Because treatment of head and neck cancers is complex and involves multiple modalities, a multidisciplinary approach is needed. This review focuses on the goal of organ preservation and postoperative treatment of high-risk patients with the concurrent use of chemotherapy and radiation therapy. This review also highlights recent advances in treatment using molecularly targeted therapies, specifically the role of inhibitors of the epidermal growth factor receptor in locally advanced and recurrent/metastatic squamous cell cancer of the head and neck. Studies in the English language were identified by searching the MEDLINE, EMBASE database (1980-2007) using the search terms head and neck, squamous cell, carcinoma, chemotherapy, radiation, human papillomavirus, epidermal growth factor receptor, and targeted therapy.