Oral cancer is arguably the most serious condition that dental providers may encounter in their practice. The relatively poor prognosis associated with oral cancer highlights the importance of the dental team's awareness of the disease. While many characteristics of oral cancer have endured over time, new research is revealing trends that are changing the way we approach its screening, diagnosis and treatment. In this report, we provide a translational overview of oral cancer, including risk factors, signs and symptoms, clinical management, as well as our recent findings on the role of chronic inflammation in the development of the disease. In addition, our recent genetic profiling approach in both cancer cell lines and in patients has identified potential biomarkers, molecular pathways and therapeutic drugs (Velcade and Aspirin) for oral squamous cell carcinomas. This comprehensive review should be of interest to all dental professionals.