This paper reviews the in vitro digestion models developed to assess the stability digestion of food allergens, as well as the factors derived from the methodology and food structure that may affect the assay results. The adequacy of using the digestion stability of food allergens as a criterion for assessing potential allergenicity is also discussed. Data based on the traditional pepsin digestibility test in simulated gastric fluid are discussed in detail, with special attention to the influence of the pH and pepsin: allergen ratio in the pepsinolysis rate. This review points out the importance of using physiologically relevant in vitro digestion systems for evaluating digestibility of allergens. This would imply the sequential use of digestive enzymes in physiological concentrations, simulation of the stomach/small intestine environment (multi-phase models) with addition of surfactants such as phospholipids or bile salts, as well as the consideration of the gastrointestinal transit and the effect of the food matrices on the allergen digestion and subsequent absorption through the intestinal mucosa. In vitro gastrointestinal digestion protocols should be preferably combined with immunological assays in order to elucidate the role of large digestion-resistant fragments and the influence of the food matrix on the stimulation of the immune system.