Endoscopic detection of gastrointestinal cancer currently depends in large part on white light images, which show mucosal surface changes in real time. Molecular imaging is a rapidly growing new field in gastrointestinal endoscopy, which could provide additional information about molecular expression of cells and processes involved in cancer biology. It uses the molecular signature of cells for minimally-invasive, targeted imaging of gastrointestinal pathologies. Exogenous fluorescent agents serve as molecular beacons and include labeled peptides and antibodies, and probes with tumor-specific activation. An advantage of molecular imaging in digestive tract is the opportunity to apply such agents topically, overcoming the hurdles for delivery of these agents to the region of involvement, including immunogenic reaction and potential toxicity. Recently developed molecular targets include proteolytic enzymes, endothelial-specific markers, and apoptosis reporters. Molecular imaging has the potential to greatly impact on future endoscopy in gastroenterology.