Human milk contains health-promoting microbes, growth factors, and other components that regulate host-microbe interactions, which are considered protective and seem to have a key role in infant health. The microbial composition of human milk is likely influenced by genetic factors, mode of delivery, and maternal nutrition and may differ among feeds, time of day, lactation stage, and between mothers and populations. Little is known about the impact of these factors on the human milk microbiome. This chapter provides an overview of the perinatal factors that probably influence the composition of the human milk microbiome, such as maternal health, time postpartum, mode of delivery, and gestational age, and their potential biological relevance. Our increasing understanding of which and how various perinatal factors influence the milk microbiome may provide new dietary tools and strategies targeted to modulate milk microbiome and impact infant microbial colonization and short-and long-term health effects.