Colorectal cancer (CRC) is the second most common lethal cancer in the Western world. There is a 10 to 20 years lead time from normal mucosa to carcinoma which offers a window of opportunity to modify and prevent the outcome of CRC, with its incipient morbidity and mortality. The objective of this paper is to review the evidence for chemoprophylaxis in CRC, identify currently used agents and determine their role in the current management algorithm of CRC. Large cohort-control and randomised controlled trials in the most studied chemoprophylaxis agents are reviewed. Currently, the role for chemoprophylaxis in CRC remains a niche area, with celecoxib the only recommended agent for use in patients with familial polyposis syndromes. However, the role of chemoprophylaxis is likely to grow significantly in the next decade as understanding of the stepwise tumorigenesis cascade becomes better understood and current clinical trials are completed.