Contrary to common belief, the human neonate is often born with a non-sterile gastrointestinal tract, suggesting fetal colonization. When fed milk from the mother’s breast the infant derives a set of live microbes that have the capability of colonizing the gastrointestinal tract. This milk also provides a source of enzymes such as lipase and alkaline phosphatase. Milk also provides a multitude of proteins, microRNAs and other components that putatively interact with the host intestinal innate mucosal immune system to control infection, modulate intestinal inflammation, and provide signaling to distal sites for development of adaptive immunity as well as growth and communication with the central nervous system. Live microbes found in fresh mother’s milk may be personalized for her infant, and thus provides an impetus for either ensuring delivery of this personalized milk to the infant or if that is not possible, to develop the means to personalize donor milk or formula.