The posterior commissure of the anal canal is less well perfused than the other segments of the anoderm. There is growing evidence that the increased activity of the internal anal sphincter, which is found in almost all patients with a chronic anal fissure, further decreases the anodermal blood supply, especially at the posterior midline. Reduction of anal pressure, either by anal dilatation or by lateral internal sphincterotomy, is the most important step in the treatment of chronic anal fissure. However, both procedures frequently result in permanent sphincter defects and subsequent continence disturbances. Recently, nitric oxide (NO) has been identified as the chemical messenger mediating relaxation of the internal anal sphincter. It has been shown that local application of exogenous NO donors such as nitroglycerin and isosorbide-di-nitrate reduces anal pressure and improves anodermal blood flow. This dual effect results in fissure healing in more than 80% of patients.