Cow's milk allergy (CMA) is the most frequent food allergy in early childhood, occurring during the first months of life. Despite its spontaneous benign evolution, CMA is still problematic, since diagnosis remains unsafe and the prediction of clinical outcome and time of appearance of oral tolerance (OT) is difficult. The acquisition of OT is of 45-56% at 1 year; 60-77% at 2 years and about 90-95% after 5 to 10 years. The concept of OT is a mechanism of immunological regulation, which consists of a modulation of the systemic immune response to oral proteins. The main actors of OT are: antigens, digestive mucosal, antigen-presenting cells and T-Iymphocytes. The most common food allergens are cow's milk, soy and egg proteins, as well as fish and seafood products and peanuts. Two types of oral tolerance exist: primary, which is the induction of tolerance to a formerly unknown antigen; and secondary, which is a re-induction of OT to an antigen. The role of eviction of antigens and of partially hydrolyzed formulae was largely studied for primary tolerance. For secondary OT, patients must receive a cow's milk-free diet and extensively hydrolyzed formulae until its spontaneous appearance, which, as shown in a recent study, seems to be quicker with the use of oligopeptides rather than amino acids.