Confocal microendoscopy permits direct observation of pathologic change at the microscopic level rather than traditional inference based on indirect changes at the macroscopic (cell) level. The main benefit includes earlier detection of precancerous and cancer conditions through improved biopsy selection and examination and more cost-effective solutions to screening and surveillance. Numerous outstanding research and commercial groups with varying approaches to confocal microendoscopy are allocating significant efforts to making the technology commercially available. The initial instruments will likely be geared toward screening for and surveillance of esophageal and colon-related conditions. Future developments related to greater functionality, improved ease of use, and automated analysis are likely to facilitate adoption and use of the technology. Clinical gastroenterologists should look forward to the potential of confocal microendoscopy as a logical and needed modality to advance the field of gastroenterology.