Antibiotics have been commonly used in Crohn's disease despite a lack of controlled data to support their use. Review of the histology and histopathology favor an infectious origin and increased infectious complications are witnessed in Crohn's patients. Enhanced permeability may play a role in providing access of enteric organisms or their cell wall derivatives to the intestinal mucosa. Through an understanding of the pathophysiology and the important role of the fecal stream along with a critical review of the literature, we may gain a better understanding of the role of antibiotics in Crohn's disease.