The clinical relapse rate after surgery for Crohn's disease in prospective studies is about 40% at 2 years in people who receive no postoperative prophylaxis. Thiopurines (azathioprine and 6-mercaptopurine) are likely to be the most effective pharmacotherapy for preventing postoperative relapse: about four patients need to be treated for 2 years to prevent one clinical relapse. The factors that help to identify patients at highest risk of relapse are discussed, along with the reasons for the choice of thiopurine, dose and duration of therapy. Other measures to reduce the relapse rate are addressed.