Confocal laser endomicroscopy (CLE) has been recently proposed as a new technique that allows in vivo histologic assessment of mucosa during endoscopy. The most commonly used contrast agents are acriflavine hydrochloride and fluorescein sodium. For colon pathology assessment, the administration of fluorescein intravenously produces a strong staining of both surface epithelium and deeper layers of lamina propria. Confocal laser endomicroscopy is a feasible method to diagnose colon cancer in vivo. Furthermore, confirmation of neoplastic changes using CLE during colonoscopy may lead to major improvements in the clinical management of the patients with inflammatory bowel disease. Biopsies can be limited to targeted sampling of relevant lesions. Confocal laser endomicroscopy will certainly play an important diagnostic role during gastrointestinal endoscopy in the future, enabling the elimination of the diagnostic delay associated with conventional biopsy preparation and processing.