Multimodality imaging is an essential aspect of endoscopic surveillance for the detection of neoplastic lesions, such as dysplasia or intramucosal cancer, because it improves the efficacy of endoscopic surveillance and therapeutic procedures in the gastrointestinal tract. This approach reveals mucosal abnormalities that cannot be detected by standard endoscopy. Currently, these imaging techniques are divided into those for primary detection and those for targeted imaging and characterization, the latter being used to visualize areas of interest in detail and permit histological evaluation. This Review outlines the use of virtual chromoendoscopy, narrow-band imaging, autofluorescence imaging, optical coherence tomography, confocal endomicroscopy and volumetric laser endomicroscopy as new imaging techniques for diagnostic investigation of the gastrointestinal tract. Insights into use of multimodal endoscopic imaging for early disease detection, in particular for pre-malignant lesions, in the oesophagus, stomach and colon are described.