So far, the relevance of NOD2/CARD15 genotyping for clinical practice is modest. The current data almost unanimously show that NOD2/CARD15 mutations in Crohn's disease are associated with small-bowel involvement. More studies are needed to determine whether NOD2/CARD15 mutations are also associated with a fibrostenotic behaviour of the disease. If CARD15 variants would predict a more aggressive disease course, then a more aggressive treatment is justified in these patients after NOD2/CARD15 genetic testing. It is not clear whether NOD2/CARD15 genotyping is helpful in differentiating indeterminate colitis patients. Although CARD15 variants do not predict response to the TNF alpha monoclonal antibodies, the role of the gene in response to other drugs is not known. Finally, screening unaffected relatives of CD patients is not recommended until preventive strategies are available.