Recent research has suggested that a family of antimicrobial and inflammatory molecules, called beta-defensins, are involved in the etiology of Crohn's disease. In this issue, Bentley and colleagues provide data that disagree with previous studies. They show that the beta-defensins that are copy number polymorphic have, on average, higher genomic copy number in patients when compared with healthy controls. This editorial places these new data in the context of previous research on the genetics of beta-defensin copy number polymorphism and association with Crohn's disease. It also suggests a path allowing this research area to move forward with confidence.