Neonatal immune system faces considerable challenges as it must cope with antigenic stimulus following gut and skin bacterial colonization, and exposure to numerous new environmental antigens while organs are developing, requiring low inflammation to allow harmonious growth. In addition to its impact on child growth and prevention of infectious disease, breast-milk may help to educate the immune system towards acceptance of non 'dangerous' antigens. Indeed, epidemiological studies report that breastfeeding protects from immune-mediated diseases such as allergy, celiac disease and type-1 Diabetes. However, data are controversial and mechanisms unclear. Here we will present and discuss experimental data indicating that breastfeeding-induced protection may rely on immune tolerance induction in the breastfed child upon antigen transfer through maternal milk. The tolerogenic potential of breast milk depends on maternal exposure to common environmental and dietary antigens and the efficiency of antigen transfer across mammary epithelium. Induction of tolerance upon breast-milk mediated antigen transfer will also depend on the presence of immunomodulatory factors in breast-milk and of its impact on neonatal gut and immune system maturation. Better understanding of maternal influence on tolerance induction by antigen transfer through breast milk should allow the development of new strategies for prevention of immune mediated diseases.