Endomicroscopy is a new imaging tool for gastrointestinal endoscopy. In vivo histology becomes possible at subcellular resolution during ongoing colonoscopy. Panchromoendoscopy with targeted biopsies has become the method of choice for surveillance of patients with inflammatory bowel disease. Endomicroscopy can be added after chromoendoscopy to clarify whether standard biopsies are needed. This smart biopsy concept can increase the diagnostic yield of intraepithelial neoplasia and substantially reduce the need for biopsies. Clinical acceptance is increasing because of a multitude of positive studies about the diagnostic value of endomicroscopy. Smart biopsies, functional imaging, and molecular imaging may represent the future for endomicroscopy.