The present review is an attempt to summarize the important advances made during the last decade in the molecular approach to oral cancer and its application for early, sensitive diagnosis, effective treatment, and improved prognosis. Cancer of the oral cavity is more prevalent in developing countries, where many people are addicted to tobacco chewing and maintain poor oral hygiene. Despite extensive research on the biological and molecular aspects of oral SCC, the problems of local-regional recurrence and distant metastasis still persist. Among the more pressing problems in clinical management is the lack of early detection, due to the absence of a potential diagnostic marker. Oncologists are now more aware of the challenges associated with the treatment of cancer of the oral cavity, and survival percentages are improving significantly. More trials are need in the area of improved surgical procedures, variations in dosages of radiotherapy, and the use of various combinations of chemotherapeutic agents with minimal side effects. Moreover, progress in the elucidation of the molecular genetic changes that lead to the development of these tumors should soon bring novel diagnostic and therapeutic procedures into clinical practice. The case of ONYX-015 is one example of success, which has shown the great potential in Phase-I and II clinical trials. Finally, the legislator should also impose some restrictions and bans on the easy availability of various forms of tobacco.