The advances in the understanding of the host–microbes interactions suggest that maternal microbiota plays a crucial role in infant health. Microbial colonization is essential for the immune system development and function. Intestinal microbes also affect other physiologic processes related to nutrition and metabolism and also, have a relevant impact on the regulation of the intestinal homeostasis and interacting with the immune system and beyond. Human microbial colonization begins at birth when the newborn is exposed to the maternal microbiota and continues throughout lactation although this process is also modulated by perinatal factors including mode of delivery, antibiotic exposition and infant diet. Maternal microbiota forms the first and unique microbial inoculums, and from birth onwards, the microbial diversity increases and converges towards an adult-like microbiota by the end of the first years of life. Alterations in this microbial colonization process are strong risk factors for the development of some diseases during life. Taken all information available, an adequate nutritional and microbial environment during the perinatal period is key in promoting and supporting human health. This knowledge may provide a window of opportunity to reduce the risk of non-communicable diseases in infants at risk using targeted strategies aimed at modulating the microbiota during early life.This lecture aims to provide an overview of maternal-infant microbiota and potential factors contributing to microbial colonization with impact on infant health at short and long term.