The postnatal period represents a particularly dynamic phase in the establishment of the host-microbial homeostasis. The sterile protected intestinal mucosa of the fetus becomes exposed to and subsequently colonized by a complex and diverse bacterial community. Both, the exposure to microbial ligands and the bacterial colonization have been described to differ between neonates born vaginally or by cesarean delivery. These differences might influence the development of the mucosal immune system, the establishment of a stable intestinal host-microbial homeostasis, and ultimately contribute to the risk to acquire immune mediated diseases later in life. Indeed, an increased risk for atopic diseases such as allergic rhinitis and asthma was reported in children born by cesarean delivery. Our recent study described an association between cesarean delivery and celiac disease. Here we summarize the available information on postnatal microbial colonization and the influence of the mode of delivery on flora composition and host microbial homeostasis. We discuss possible consequences of the mode of delivery on epithelial barrier function and the establishment of the mucosal immune system and speculate on functional links between flora alterations and the development of inappropriate host immune responses that may contribute to enteric inflammatory diseases.