Crohn's disease (CD) is one of the two major forms of inflammatory bowel disease (IBD). Although the etiology of CD is unclear, many experimental and clinical observations support the potential role for intestinal microflora in the pathogenesis of CD. Manipulation of the luminal content using antibiotics may therefore represent a potentially effective therapeutic option. Some randomized controlled trials have demonstrated the efficacy of these drugs in treating the perianal disease, inducing and maintaining of CD remission and decreasing CD recurrence rates in operated patients. However, the use of antibacterial therapy for CD is also controversial, even this approach is frequently and successfully adopted in clinical practice. Fairly narrow indications for antibiotics are suggested by current management guidelines. Large studies are required to better define the role of antibacterial agents and combination regimens in CD. Broadwcjd spectrum antibiotics, such as metronidazole, fluoroquinolones and rifaximin, are widely used to treat CD, and their effects have been recognized. Because of the lack of adequate theoretical support and adverse drug reactions, the reasonable application of antibiotics to treat CD is still a clinical problem. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.