This is a review of the experience obtained at the Institute Gustave Roussy, evaluating the role of chemotherapy and of altered fractionated radiotherapy in locally advanced head and neck cancer. The database included nearly 120 randomized trials, and about 25,000 patients, with a median follow-up of 6 years. In the chemotherapy database (Meta-Analysis of Chemotherapy in Head, Neck Cancer and Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma), concomitant cisplatin-based radiotherapy-chemotherapy provided the most significant benefit on locoregional control and survival, both in head and neck squamous cell carcinomas and nasopharyngeal carcinomas. In head and neck squamous cell carcinomas, the benefit of adding concomitant chemotherapy was found to be in the same order of magnitude whether radiotherapy was postoperative or definitive. In the altered radiotherapy database (Meta-Analysis of Radiotherapy in Carcinoma of Head and Neck), among the different types of altered fractionated radiotherapy, hyperfractionation provided the most significant benefit. The benefit associated with altered fractionated radiotherapy and of concomitant chemotherapy markedly decreased with increasing age. This database provided a unique tool to evaluate long-term effects of chemotherapy and altered fractionated radiotherapy in head and neck cancer. This allowed the oncological community to obtain a reliable characterization of the magnitude of the treatment benefits in this type of cancer and to base patient care and future research on strong evidence.