Several lines of evidence link inflammatory bowel diseases to modifications of intestinal microflora. Epidemiologic and clinical data suggest a triggering role for select agents in ulcerative colitis and in Crohn disease. Experimental evidence indicates that intestinal microorganisms are needed for developing intestinal inflammation in IL-10 knockout mice, and this is associated with an increased number of adherent clostridia and a decrease of lactobacilli and bifidobacteria. It may be hypothesized that a host–agent-specific relationship leads to an abnormal immune response, which may be genetically driven in select inflammatory bowel diseases. However, different from adults, the pattern of intestinal microflora undergoes profound changes during the early stage of life, contributing to the development of the immune system. A close relationship exists between microbiologic and immunologic imprinting. The microbiologic imprinting in neonates may be modified using bacterial probiotics that colonize the intestine, modify the immune response, and decrease the risk for atopy. Probiotics may decrease the recurrences of inflammatory bowel diseases. Preliminary evidence of intestinal antiinflammatory effects has been detected in children with cystic fibrosis. Overall these data provide the rationale to investigate the interaction between intestinal microflora and the local and general immune response in children with, or at risk for, inflammatory bowel diseases. This approach may be a key for understanding the pathophysiology of intestinal inflammation and may disclose novel strategies to educate better the immune system, particularly during its developmental stage.