Introduction: Postoperative recurrence after surgery for Crohn's disease (CD) is virtually inevitable, and its mechanism is poorly known.Aim: To review the numerous factors involved in CD postoperative recurrence (POR) pathogenesis, focusing on single immune system components as well as the immune system as a whole and highlighting the clinical significance in terms of preventive strategies and future perspectives.Methods: A systematic literature search on CD POR, followed by a review of the main findings.Results: The immune system plays a pivotal role in CD POR, with many different factors involved. Memory T-lymphocytes retained in mesenteric lymph nodes seem to represent the main driving force. New pathophysiology-based preventive strategies in the medical and surgical fields may help reduce POR rates. In particular, surgical strategies have already been developed and are currently under investigation.Conclusions: POR is a complex phenomenon, whose driving mechanisms are gradually being unraveled. New preventive strategies addressing these mechanisms seem promising. [ABSTRACT FROM AUTHOR]