Microbial colonization during the neonatal period and infancy can have long-term consequences for the health and immunity of the individual. Several factors influence the development of the infant microbiome, such as mode of delivery, type of feeding, dietary changes, and antibiotic use. The infant microbiome exhibits high plasticity and adaptability, thus providing a window of opportunity for inducing appropriate interventions and alterations to improve overall health. Maintenance of host-microbiome homeostasis is very important as when this homeostasis is disrupted, it leads to aberrant outcomes. The microbiome has a crucial role in the maturation of the immune system and providing immunity against infections in early life. Furthermore, in utero microbial stimulation, mostly through the maternal gut microbiome, has been found to influence prenatal and postnatal immune cell development. Studies of germ-free animals have revealed significant information on the importance of the microbiome in the development of the immune system in early life. Recent studies have revealed a crucial time window in early life during which appropriate microbial exposures need to take place for proper immune cell development. Appropriate microbial exposures during this time window are also associated with reduced risk of development of various diseases, such as allergic diseases, asthma, inflammatory bowel disease, and diabetes in later life. A better understanding of how the neonatal microbiome develops and its role in the development and maturation of the immune system in early life could help us in devising effective strategies to prevent various health disorders. © 2022 Elsevier B.V., All rights reserved.