Colorectal cancer is one of the leading causes of death worldwide. The progression from adenoma to cancer is a well known phenomenon. Current clinical practice favors colonoscopy as the preferred modality for colorectal cancer screening. Many novel endoscopic technologies are emerging for the purposes of performing "optical biopsy" to allow real-time histologic diagnosis of polyps. High resolution microendoscopy is a low-cost endoscopic technology that has demonstrated high sensitivity and specificity in differentiating neoplastic and non-neoplastic polyps. With the ability to make real-time conclusions based on the endoscopic appearance of polyps, it is becoming increasingly possible to decrease the rate of unnecessary polypectomies and utilize a "resect and discard" strategy to decrease costs of pathology evaluation. Future directions for this technology include surveillance of premalignant conditions such as inflammatory bowel disease. Moreover, the low cost and relative ease of use of this technology lends itself to widespread applicability.