Discerning the genetics of hereditary colorectal cancer syndromes has enabled a more individualized approach to preventing and treating colorectal cancers in affected patients and families. As these syndromes carry significant risk of colorectal cancer (nearly 100% in some cases), prophylactic colectomy is an important option for preventing cancer. This article addresses the rationale and indications for prophylactic colectomy in hereditary colorectal cancer syndromes, and provides insight into the details of surgical management. J. Surg. Oncol. 2015 111:112–117. © 2014 Wiley Periodicals, Inc.