In patients with inflammatory bowel disease, a dissociation can occur between symptoms and presence of inflammatory lesions. This dissociation has led to the recognition that objective measures of disease activity together with clinical assessment should be co-primary endpoints in clinical trials. Objective assessment of inflammatory lesions has classically relied on ileocolonoscopy. However, examination with endoscopy cannot always be complete and does not evaluate transmural changes. Furthermore, histological alterations may persist in the presence of mild or even absent endoscopy lesions. For these reasons cross-sectional imaging, particularly magnetic resonance imaging [MRI] and histology, are being considered as potential new tools for objective assessment of lesions. In patients with Crohn's disease, it has been shown that MRI has a high degree of accuracy for the evaluation of presence and severity of inflammation, and that validated indices of activity such as the Magnetic Resonance Index of Activity [MaRIA] are responsive to effective therapeutic interventions. In the context of clinical trials, MRI may help in patient selection by providing always a complete assessment of the small bowel and colon and detecting the presence of complications. A generally accepted definition of histological mucosal healing, to be used in clinical trials on Crohn's disease or ulcerative colitis, does not exist. Several histological scoring systems are available, most of these based on the evaluation the presence of neutrophils, epithelial cell damage, and an increase in lymphocytes and plasma cells. At present, histological remission is not included as primary endpoint for therapeutic trials, but better outcomes associated with achievement of histological healing favours the consideration of histology as an endpoint in the future.