Diseases due to defect in tolerance induction such as allergy, celiac disease, or Type 1 Diabetes develop mostly in childhood indicating the necessity of early intervention for primary prevention. Epidemiological studies report that breastfeeding could protect from these diseases. However, data are controversial and the mechanisms unclear. Experimental data suggest that breastfeeding-induced protection might rely on tolerance induction as long as some criteria are fulfilled. Thus, the tolerogenic potential of breast milk would depend 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. The better understanding of maternal influence on tolerance induction through breastfeeding should allow the development of new strategies to prevent immune-mediated diseases.