Squamous cell carcinoma of the head and neck requires a multidisciplinary management. Risk factors for adjuvant radiotherapy are stage III-IV, perineural involvement or vascular tumor embolism. If there are positive margins or extracapsular extension chemoradiotherapy is needed. For patients with nonresectable disease we recommend treatment with concomitant chemoradiation, although this has important acute and late toxicity. Concomitant EGF receptor inhibitors and taxane-based induction chemotherapy are new strategies under study that have demonstrated some benefits but are not yet the standard treatment. Intensity-modulated radiotherapy allows one to decrease radiation dose to organs. Preclinical work in signaling pathways and other oncogenic factors (e.g., human papillomavirus infection) will be the key to improving outcomes of head and neck cancer patients in the future.