The neonate and infant possess an immature immune system, with significant deficiencies in the innate and adaptive arms of the immune system, as well as a relatively permeable and nearly sterile gastrointestinal (GI) tract. These developmental factors play a prominent role in the increased risk of infection in the first year after birth. Fortunately, human milk possesses a diverse microbiota and a multitude of substances and components that immediately compensate, in part, for these immunologic and anatomical factors. Moreover, continued exposure to the combination of cells, numerous bioactive factors, and microbiota present in human milk induces lifelong effects not only in the newborn’s or infant’s immune system but also in nearly every other organ system.