Cronkhite–Canada syndrome (CCS) is a rare, non-inherited gastrointestinal polyposis syndrome associated with characteristic ectodermal abnormalities. A number of potentially life-threatening complications including malnutrition, gastrointestinal bleeding and infection may occur in affected patients and CCS is fatal in many cases. The optimal therapy for CCS is not known but several treatment options have been described. Nutritional support, antibiotics, corticosteroids, anabolic steroids, histamine-receptor antagonists and surgical treatment have all been used with varying degrees of success. Unfortunately, controlled therapeutic trials have not been possible because of the rarity of the disease. Most recently, a combination regimen using histamine-receptor antagonists, cromolyn sodium, prednisone and suppressive antibiotics has been described. The reported treatment options and rates of success are reviewed.