Locally advanced squamous cell cancer of the head and neck is a major contributor to morbidity and mortality worldwide. Despite progress through the use of multimodality treatment involving surgery, radiotherapy, and chemotherapy in recent years, the survival remains poor, and treatment-related morbidity-mainly caused by radiation-induced effects such as soft tissue scarring, esophageal stenosis, xerostomia, dental decay, and osteoradionecrosis-is a major problem in long-term survivors. Data from early trials and encouraging results from meta-analyses have revived interest in the use of neoadjuvant or induction chemotherapy before definitive local treatment. Recent randomized trials have demonstrated marked improvements in survival with the addition of the taxane docetaxel (Taxotere) to the traditional induction regimen consisting of cisplatin and 5FU (TPF) compared with cisplatin and 5FU (PF) alone and have established a new standard of care. The newer TPF induction chemotherapy regimens also appear to be tolerated better than PF when accompanied by adequate supportive measures. Studies to enhance the efficacy of TPF induction chemotherapy by adding new targeted agents, such as the EGF-R inhibitors cetuximab and panitumumab, are underway.