Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Many, if not most, cases arise from premalignant lesions (adenomas) which may be identified and removed prior to becoming frankly malignant. For over a decade, colonoscopy has been the preferred modality for both CRC screening and prevention in the US. Early reports suggested that colonoscopic screening imparted a 90% risk reduction for colorectal cancer. Subsequent studies showed that estimate to be overly optimistic. While still an outstanding CRC screening and detection tool, colonoscopy has several important limitations. Some of these limitations relate to the mechanics of the procedure such as the risk of colonic perforation, bleeding, adverse consequences of sedation, and the inability to detect all colonic polyps. Other limitations reflect issues with patient perception regarding colonoscopy which, at least in part, drive patient non-adherence to recommended testing. This review examines the literature to address several important issues. First, we analyze the effect of colonoscopy on CRC incidence and mortality. Second, we consider the patient-based, periprocedural, and intraprocedural factors which may limit colonoscopy as a screening modality. Third, we explore new techniques and technologies which may enhance the efficacy of colonoscopy for adenoma detection. Finally, we discuss the short and long-term future of colonoscopy for CRC screening and the factors which may affect this future.