Colorectal cancer (CRC) contributes a major burden of cancer mortality in the United States. There are multiple effective screening approaches that can reduce CRC mortality. These approaches are supported by different levels of evidence, and each has its own advantages and disadvantages. Implementing a systematic approach to screening that addresses the multiple steps involved in the screening process is essential to improving population-level CRC screening. Offering patients stool-based screening is important for increasing screening uptake. However, programs that offer stool testing must support the population health infrastructure needed to promote adherence to repeat testing and follow-up of abnormal tests.