The Microbiome in Prenatal and Neonatal Life clarifies that the microbiome in the maternal fetal unit and immediate changes that occur as new microbes are acquired postnatally play major roles in subsequent health and disease. Rapidly developing technologies for multi-omic analyses and systems biology are shifting paradigms in both scientific knowledge and clinical care with regard to this topic. In essence, we are changing the idea that newborns emerge from sterile environments. As such, in-utero colonization may have impacts on the development of immunity and metabolism that, with epigenetic modifications, will lead to diseases in later life. In addition, the microbial profile that develops during and after birth depends on mode of delivery, type of feeding (human milk versus formula), and various other environmental factors to which the newborn is exposed. • Discusses the critical nonredundant timeframe in a newborn's life during which many factors drive immune and tissue maturation and influence the susceptibility to immune-mediated and other diseases in adult life• Proves that the fetus and uterine membranes are exposed to not only microbes in close proximity but also to microbial products from metabolism of microbes in the mother• Shows that since early life periods are a critical window for development, epigenetic and/or immunologic alterations may occur that can affect not only the infant during his/her lifetime but also subsequent generations• Gives insight into factors that may affect the newborn microbiome and subsequent development