Inflammatory bowel diseases (IBD) represent a global phenomenon, with a continuously rising prevalence. The strategies concerning IBD management are progressing from clinical monitorization to a targeted approach, and current therapies strive to reduce microscopic mucosal inflammation and stimulate repair of the epithelial barrier function. Intestinal permeability has recently been receiving increased attention, as evidence suggests that it could be related to disease activity in IBD. However, most investigations do not successfully provide adequate information regarding the morphological integrity of the intestinal barrier. In this review, we discuss the advantages of confocal laser endomicroscopy (CLE), which allows in vivo visualization of histological abnormalities and targeted optical biopsies in the setting of IBD. Additionally, CLE has been used to assess vascular permeability and epithelial barrier function that could correlate with prolonged clinical remission, increased resection-free survival, and lower hospitalization rates. Moreover, the dynamic evaluation of the functional characteristics of the intestinal barrier presents an advantage over the endoscopic examination as it has the potential to select patients at risk of relapses. Along with mucosal healing, histological or transmural remission, the recovery of the intestinal barrier function emerges as a possible target that could be included in the future therapeutic strategies for IBD.