A wide range of clinical syndromes exist that are related to adverse reactions to dietary proteins and that affect predominantly the gastrointestinal tract of infants and children. Experimental data suggest a critical role for developmental alterations affecting intestinal permeability and the mucosal immune response that predispose to these conditions. The diagnostic and therapeutic approach to these disorders varies depending on the nature of the presumed offending antigen, the anatomic site affected, the severity of the inflammatory process, and the implications for future dietary and medical management. Ultimately, the proof that a particular dietary antigen is responsible is dependent on observing the response to oral challenge.