Head and neck cancer is the fifth most common cancer worldwide but the most common malignant disease site in central Asia. The treatment of head and neck cancer is one of the most challenging in clinical oncology because of the high content of hypoxic cells of the cancer which increases resistance to therapy and also because of the high capacity of the cancer to regrow during treatment. For unresectable tumours, radiotherapy and chemotherapy alone or more often in combination is the treatment of choice. The aim of this paper is to review current understanding of carcinogenesis of head and neck cancer in relation to predisposing risk factors in general and for specific sub-sites and how these risk factors interact with the main reported genetic alterations in the progression of the cancer. The implications of these changes in determining choice of therapy are also discussed from a brief historical perspective of the various treatment approaches of head and neck cancer.