Immediately after birth the mucosa of the gastrointestinal tract, which represents the greatest body surface area exposed to the outside environment, is confronted with a large variety of foreign antigens. The immune system of the intestine now has to meet the task of discriminating between pathogens and harmless antigens, such as food proteins and commensal bacteria, and to respond accordingly. This important job is fulfilled by cells of the gut-associated lymphoid tissue, the largest immunologic organ in the body. Despite the large extent of food antigen exposure, only a small percentage of individuals experience adverse immunologic reactions to food. This is due to the fact that the normal immune response to dietary proteins is associated with the induction of oral tolerance, which refers to a state of active inhibition of immune responses to an antigen by means of prior exposure to that antigen via the oral route. Abrogation of oral tolerance or failure to induce oral tolerance may result in the development of food hypersensitivity. In the present review, factors that may play a role in the outcome of oral tolerance versus sensitization to food proteins are discussed. © 2006 Elsevier Masson SAS. All rights reserved.