When diagnosed at a locally advanced stage head-and-neck carcinomas require a multidisciplinary management. Primary surgery should be followed by the concomitant delivery of adjuvant radio- and chemotherapy, which is nowadays considered as the standard approach. A number of operable cases can be treated according to organ preservation programmes as well. Unresectable disease, the prognosis of which remains dismal, is typically treated with chemo-radiation too, but with the advent of taxanes, induction chemotherapy is currently revisited. Novel targeted therapies yielded encouraging results, when combined with irradiation, because of lower toxicity index than chemotherapy.