Surgery and radiotherapy are generally not an option for recurrent/metastatic head and neck squamous cell carcinoma. Chemotherapy is the only possible treatment. The five major drugs active in monotherapy are methotrexate, cisplatin, 5-fluorouracil (5-FU), cetuximab (an antiepidermal growth factor receptor antibody) and taxanes (paclitaxel or docetaxel). They allow 10-25% response with a median survival of approximately 6-8 months. Various chemotherapy doublets may achieve higher response rates, up to 45-50%, but overall survival remains unchanged. As recurrent patients are often symptomatic, better response is associated with better quality of life and the standard treatment for patients with performance status 0-1 is the combination of cisplatin and 5-FU. Recently, the triplet cisplatin-5-FU-cetuximab, which has been shown to result in an increased response rate and a significantly better median survival of 10.4 months, has become the new treatment standard.