Gastrointestinal (GI) tract malignancies have a tremendous impact on society. Colorectal cancer is the second leading cause of cancer death in the United States and accounts for 10% of all cancer deaths. Significant research efforts are being directed toward using the interaction of light and tissue to detect pre-cancerous lesions of the GI tract. This article reviews the current status of various experimental optical technologies to detect pre-cancerous changes in the GI tract and focuses on the clinical applications of these technologies for the practicing gastroenterologist.