Food protein-induced enterocolitis syndrome (FPIES) represents a non-IgE-mediated food allergic disorder with delayed gastrointestinal symptoms that may evolve in a medical emergency. Clinically, FPIES can be distinguished into acute and chronic phenotypes. FPIES is mainly diagnosed in infancy however the onset at older ages is being progressively described. The pathogenetic mechanism underlying FPIES remains mainly unexplained, but an alteration of food-specific T-cell response has been proposed. The diagnosis of FPIES is primarily clinical, since there are not available specific biomarkers. Oral food challenge (OFC) is the gold standard for diagnosing FPIES or excluding the onset of tolerance to the triggering food. Management of FPIES includes an acute phase treatment and a maintenance therapy with the strict food avoidance until challenge, in order to prevent new attacks and avoid nutritional alterations. Acute management requires hydration that can be performed orally or intravenously according to clinical status. Long-term management of FPIES is based on the avoidance of the culprit food(s) and supervised introduction of other high-risk foods if never taken before among infants before 12 months of age. There is a compelling need of future achievements in FPIES research for the definition of underlying disease pathogenesis and potential therapeutic point of care.