Genetic testing for cancer susceptibility has been implemented widely in recent years, with the hope that it eventually will lead to a reduction in cancer-related mortality. Asymptomatic individuals who have a genetic predisposition for cancer can be identified, and many may benefit from early intervention. Not all of these individuals will develop cancer, however, and the penetrance varies among individuals with different mutations. Surveillance, chemoprevention, and prophylactic surgery are accepted options for managing individuals who have a genetic predisposition for cancer. Yet, there are no randomized prospective trials that have assessed the impact of these interventions specifically in mutation carriers. The decision to undergo prophylactic surgery therefore should be made after all other management options are considered, and the patient is informed of the potential risks and benefits of surgery. This article provides an overview of the role of prophylactic surgery for managing patients who have a genetic predisposition for cancer. It specifically discusses the potential role of surgery in preventing breast, colon, thyroid, and gastric cancers. Additionally, it discusses the types of prophylactic surgical procedures that are performed commonly, and their expanding role in cancer prevention.