Confocal laser endomicroscopy (CLE) is a new technique allowing during ongoing endoscopy microscopic subsurface examination of the digestive mucosa. CLE is based on tissue fluorescence after intravenous injection of a fluorescent marker. A confocal microscope integrated into the distal tip of the endoscope generates images of the mucosa with a high level of magnification (1000 ×) comparable with histological examination. Confocal endomicroscopy can be helpful for the early diagnosis of dysplasia in patients with Barrett’s oesophagus, neoplastic changes in colonic polyps and in patients with ulcerative colitis. CLE can also be used for diagnosis of coeliac disease and early gastric cancer. This article summarizes our own experience with this revolutionary method.