Prophylactic colectomy is indicated in patients whose colons are at very high risk of developing cancer. Familial adenomatous polyposis (FAP) is the best example of a situation where prophylactic surgery is clearly necessary to prevent cancer, and has been shown to be effective in doing so. Recent advances in the molecular genetics of colorectal cancer have allowed presymptomatic diagnosis of patients with another dominantly inherited syndrome, hereditary nonpolyposis colorectal cancer (HNPCC). Prior to this, prophylactic colectomy had not been a consideration for patients in HNPCC families. A review of the outcome of colectomy and ileorectal anastomosis in FAP patients shows that although it is a major abdominal surgery there is a relatively low complication rate and the functional outcome is acceptable for a prophylactic procedure. The decision to apply colectomy to HNPCC patients depends on careful consideration of factors such as comorbidity, age, sphincter function, likely compliance with future surveillance and likely efficiency of colonoscopy as a cancer prevention strategy. In general, prophylactic colectomy is indicated in HNPCC gene carriers, because their lifetime risk for colorectal cancer is 80%.