Background: Crohn’s disease (CD) is an idiopathic, chronic, transmural inflammatory disorder of the gastrointestinal tract. Because mucosal involvement is near-universal, endoscopic healing has emerged as an important aspect in improving outcome. However, resolution of histologic disease activity has potential to convey additional benefit beyond that attained with endoscopic healing alone. Validated scoring systems of histologic disease activity are required to further assess this possibility. The aim of this study was to systematically review the existing histologic disease activity indices (HDAI) for CD and to assess their operating properties and potential use as outcome measures in clinical trials.