Crohn's disease (CD) is a chronic inflammatory bowel disease that usually progresses to bowel damage, defined as strictures, fistulas and abscesses. These complications require intestinal resection and lead to further irreversible structural damage. Cross-sectional imaging, such as magnetic resonance imaging, computed tomography and ultrasound, are accurate in assessing intestinal damage at a definite time point and the progression of damage over time. Recently, an imaging-based index, the Lémann Index, has been proposed and developed in order to quantify bowel damage in CD patients; emerging data confirm that this Index can measure the structural damage with good sensitivity to change. One challenge remains to understand whether existing or future treatments might be able to stop bowel-damage progression or even reverse intestinal damage, improving the prognosis and changing the natural history of CD. We reviewed the current data available in the literature focused on the measure of structural damage in CD patients, mainly focusing on the impact on therapies in reversing bowel damage. We also explored some further perspectives on measuring and targeting intestinal damage in clinical research and in clinical practice as an ultimate therapeutic target.