Head and neck cancer is a challenging disease. The treatment is quite complex and significant toxicity is seen with the combination of chemotherapy, radiation therapy and surgery. The present standard of care is chemoradiotherapy for most sites in the head and neck area for patients with locally advanced, unresectable disease and in patients treated for organ preservation. The recent approval of cetuximab, an EGF receptor inhibitor, for head and neck cancer in combination with radiotherapy represent an opportunity to improve the outcome for these patients, and the inclusion of this antibody within the chemoradiotherapy approaches will be studied in Phase III trials. In addition, a significant shift is occurring with the inclusion of more aggressive chemotherapy upfront, prior to chemoradiotherapy. This approach, known as sequential chemoradiotherapy, is the basis of many recently completed Phase III trials. Docetaxel, cisplatin and 5-fluorouracil appears to be the most effective induction chemotherapy regimen and is the new induction 'standard' that is being used by many cancer centres and intergroups going forward. It is also a new platform that will be used to add new targeted agents to induction chemotherapy.