Most patients with Crohn's disease will require surgery during the course of their disease. However, surgery is not curative and post-operative recurrence is quite inexorable. One year after resection up to 80% of patients have new lesions at the neo-terminal ileum and after 10 years approximately 50% of patients will experience recurrence of symptoms and 35% will need further surgery. Prevention of post-operative recurrence has, therefore, a central role in the management of Crohn's Disease. Several drugs have been evaluated to decrease the risk of both endoscopic and clinical recurrence but the overall results are largely not impressive. Among the different drugs evaluated, mesalazine, antibiotics (metronidazole and ornidazole), thiopurines and anti-TNFα antibodies have been shown to be effective whereas budesonide, probiotics and interleukin 10 are not effective. This review focuses on the actual evidence on the prevention of postoperative recurrence: randomised controlled trials and meta-analyses are critically reviewed and discussed with particular attention to the methodological aspects.