Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity syndrome that mainly affects young infants. The most common causes of FPIES are milk, soy, and grains. Studies evaluating the natural history of FPIES present heterogeneous tolerance rates, which are influenced by diverse factors, including country of origin, food triggers, atopic status, referral populations, and methodological differences in studies. FPIES to liquids (cow's milk and soy formula) generally has a favourable course with most patients developing tolerance by the age of 5 years. Acquisition of tolerance to solid foods generally occurs later. The subgroup of patients with atypical FPIES (i.e. associated positive specific IgE to culprit foods) might have a more severe phenotype and a slower acquisition of tolerance, as well as a higher risk to switch to an IgE-mediated phenotype. Further multicentric and prospective studies are needed to better establish the natural history of FPIES to individual foods, to not only determine the optimal timing of food reintroduction but also to elucidate risk factors associated with persistent FPIES.