A number of disease-specific instruments have been created over the last 30 years to assess disease activity in Crohn's disease (CD). These disease activity indices are constituted of clinical and laboratory parameters and their role in predicting disease activity and the course of disease has been reviewed various times. Currently, the severity of mucosal inflammation, assessed by endoscopy, is considered the gold standard for disease activity in CD. In the present review the most frequently used endoscopic disease activity indices and the correlation between mucosal inflammation and clinical disease activity indices, quality of life questionnaires, and biochemical markers is critically appraised. We conclude that no clinical disease activity index or single laboratory parameter of inflammation reliably predicts the mucosal inflammatory disease activity. A new, easy-to-use and robust activity index predicting mucosal inflammation is highly needed to assess the response to investigational drugs in trials and the effect of therapeutical interventions in clinical practice.