The treatment of squamous cell carcinomas of the head and neck is multidisciplinary, especially when the disease is diagnosed at an intermediate or advanced stage. Very often the clinician chooses between surgery, chemo- and radiotherapy options on the basis of the most recent data from the literature, prior experience in head and neck oncology and patient preferences. Nevertheless, for operable tumors, primary surgery, combined in poor-risk patients with radiation, is traditionally considered as the approach offering the best opportunity of cure. Randomized controlled trials and meta-analyses conducted in the 1990s have demonstrated major improvements not only in loco-regional tumor control, but also in terms of survival when chemotherapy is added to radiotherapy in the post-operative setting. The therapeutic index yielded by the co-administration of cytotoxic agents and ionizing radiation following primary surgery as compared with radiotherapy alone has nevertheless been at the center of many debates recently. Notwithstanding the fact that two randomized trials have recently provided new evidence that adjuvant chemo-radiation in poor-risk patients improves loco-regional control and disease-free survival, a number of questions regarding the optimization of the post-operative approaches remain unanswered. There is remaining need for further research efforts that would enable scientists and clinicians to improve, in the next decade, the management of this complex entity of diseases.