Chemotherapy continues to be studied intensively in head and neck cancer. Methotrexate and cisplatin remain standard agents for patients with recurrent disease. Neoadjuvant chemotherapy remains investigational with no firm evidence that it can prolong survival. It may, however, have a role in organ preservation. More recent and aggressive neoadjuvant chemotherapy regimens remain to be tested in randomized studies. Concomitant chemoradiotherapy is of high interest in this disease and is of proven benefit in randomized trials. Encouraging data from trials using protracted radiation schedules will require confirmation in randomized studies.