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Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection – at present, the sole established technique available to most of humanity – premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by microscopic techniques. In this respect, the challenging combination of autofluorescence imaging and confocal endomicroscopy seems promising, and further research is awaited.