Early-life interaction with indigenous intestinal microbes is a prerequisite for healthy immune and metabolic maturation. Human infants acquire their gut microbiota predominantly from the mother. A considerable inoculum of microbes is received by the neonate during vaginal delivery. Recent observations suggest that human gut colonization may be initiated prenatally by microbes in amniotic fluid, but the significance of this phenomenon remains unknown. After birth, neonatal gut colonization is guided by human milk factors, which selectively promote the growth of specific microbes, as well as by live microbes present in human milk. Aberrant gut colonization in early life has been associated with an increased risk of noncommunicable diseases in later life. Epidemiological and experimental studies suggest a causal relationship between early-life gut microbiota perturbations and disease risk. Perinatal antibiotic exposure, cesarean section delivery, postnatal antibiotic administration, and formula feeding, which may disrupt intestinal microecology, have been associated with disease development in later life. The modulation of gut microbiota in the perinatal period by pre- and probiotics, for example, may offer a means to reduce the risk of chronic diseases.