Colorectal cancer (CRC) is the second-leading cause of cancer mortality in the United States of America and the fourth-leading cause of cancer-related deaths worldwide. Conventional screening methods for the early diagnosis and monitoring of CRC include blood tests, endoscopy, and fecal occult blood testing (FOBT). New technologies and biomarkers from fecal studies have allowed for the development of easy, reliable, affordable, noninvasive CRC screening methods using fecal specimens. This review details the contributions of FOBT, the fecal immunochemical test (FIT), and the detection of DNA and RNA biomarkers and microbes to the development of stool-based CRC screening (Am J Transl Med 2018. 2:1–18).