The role of chemotherapy in the management of patients with head and neck cancer continues to evolve. Single-agent methotrexate or cisplatin, or the combination of cisplatin and infusional fluorouracil can be considered standard therapy for patients with recurrent disease. Neoadjuvant chemotherapy is being actively pursued. Although enhanced survival has not yet been demonstrated, the goal of organ preservation has been achieved for patients with laryngeal cancer. Because of the high incidence of locoregional failure, concomitant chemoradiotherapy is also under investigation. This treatment approach has already been suggested to result in prolonged survival in randomized studies and holds promise for the future.