In recent years, gastrointestinal endoscopy has seen an influx of high-resolution endoscopic technologies that are capable of providing optical biopsies of the epithelial surface in real time. Upcoming high-resolution endoscopy techniques are CLE, OCT, EC and HRME. Powered by automated diagnostic algorithms and more-cost effective alternatives, these high-resolution endoscopic technologies have the potential to not only facilitate real-time decision making, but also improve screening and surveillance of gastrointestinal cancers globally. This review discusses the most promising upcoming optical biopsy technologies and their clinical applications, along with the current trends, challenges and future directions.