A new paradigm in the way we envision tissue change during carcinogenesis has evolved in recent years. From a clinical standpoint, this paradigm has altered how we view “at-risk” tissue. Rather than focusing on clinical lesions, we often discuss “field” changes involving the expansion of genetically and epigenetically altered cells within a tissue, and not necessarily centered on a clinically identifiable lesion. This change reflects the recognition that genetically altered fields of cells are not always clinically or histologically apparent, yet even when occult, can constitute a significant risk. This shift in perspective has caused a management conundrum. We can use molecular techniques to characterize field changes in an extremely detailed fashion; however, such evaluation depends on identifying areas for its use. In this issue of the journal, Roblyer et al. (1) describe work with autofluorescence imaging, a field-assessment approach that may be an alternative and potential complement to lesion-focused assessments and may improve our ability to clinically distinguish normal from premalignant and malignant oral tissue in a real-time fashion. Generally, autofluorescence imaging uses higher-energy light to excite specific compounds in tissue (fluorophores) so that they re-emit lower-energy light that makes up the autofluorescence image of the tissue. The excitation light is produced by a filtered arch lamp, an array of light-emitting diodes, or a laser. Effective detection of the autofluorescence image requires blocking the excitation light from reaching the imaging sensor (camera or eye).