Anna Nowak-Wegrzyn, MD, PhD, takes a case-based approach to identify and diagnose food protein-induced enterocolitis syndrome (FPIES) in infants and how to manage acute reactions. Dr. Nowak-Wegrzyn reviews common symptoms and food triggers and discusses how to distinguish FPIES from other major non-IgE-mediated food allergies. Owing to the critical importance of avoiding nutritional deficiencies in infants with FPIES, Dr. Nowak-Wegrzyn highlights how to optimize nutritional management while proceeding with an oral food challenge. An overview of new areas of research in FPIES, including the need for better food-challenge procedures, and the burden FPIES places on families, is also presented.