Epidermoid carcinoma of the head and neck accounts for 10% of all cancers. At diagnosis, 60% of patients have a locally advanced disease, leading to high mortality and major functional handicaps. Chemotherapy has been shown to be active in patients presenting metastatic and/or locoregional recurrence, with 20 to 30% response rates, although no clearly established survival benefit has been demonstrated. Combining chemotherapy with surgery and/or radiotherapy has become possible with the development of new drugs and has recently led to major changes in management protocols for locally advanced epidermoid carcinoma of the head and neck. Therapeutic gain has been focalized on improving locoregional control, decreasing metastatic spread, and on the concept of an organ conservation strategy with schedules including chemotherapy as an inducing, concomitant, or alternating treatment with radiotherapy. Although many agents have demonstrated their efficacy, the role of chemotherapy in epidermoid carcinoma of the head and neck is not totally defined. The aim of treatment in metastatic and/or locoregional recurrent disease is palliative care. Regimens associating cisplatinum give a high response rate in patients previously untreated, without any real benefit in terms of survival. An evaluation of the activity of new agents with novel modes of action is currently under way. In locally advanced disease, concomitant chemotherapy with radiotherapy seems to give a minimal but real benefit as evidenced in the different meta-analyses recently published.