Fluorescence detection is one of a series of new spectroscopic techniques currently developed for implementation in endoscopy. This technology is likely to significantly enhance our ability to detect minute lesions and to predict the histology of certain macroscopic lesions. The two fundamental approaches to the fluorescence detection of dysplasia and early malignancy are to use tissue-specific endogenous (auto)fluorescence, and to furnish exogenous fluorophores that accumulate preferentially in neoplastic tissue. Tissue fluorescence can be detected by optical sampling of the mucosa using fluorescence spectroscopy or by taking the fluorescence information into an endoscopic image. The latter technique enables the rapid screening of large surface areas of mucosa. The clinical application of fluorescence detection in dysplasia and early cancer is still in its infancy, yet preliminary data already indicate that fluorescence imaging can indeed provide the endoscopist with real-time, accurate, non-invasive detection of dysplasia and early cancer. Furthermore, the feasibility to surpass the naked eye by detecting dysplastic lesions occult to standard endoscopy has already been established.