Premalignant lesions of the oral cavity encompass a broad range of pathology and are often comorbid in a variety of patient populations. Prompt diagnosis and management of these lesions are essential to prevent patient morbidity and mortality. The purpose of this article is to summarize and review the evaluation, screening and early detection of premalignant lesions of the oral cavity and to highlight the role of the dental team in recognizing and treating patients with these conditions, that may progress to oral cancer. In addition, a review of a non-invasive detection technique that is currently being marketed to aid general dentists and other healthcare providers for early diagnosis of potential cancerous lesions is presented. Although many studies have assessed the diagnostic accuracy of autofluorescence in oral potentially malignant disorders (OPMDs), there has been a paucity of such information in high-risk populations.