Probiotic agents have been shown to have significant clinical beneficial effects in the prevention and management of gastrointestinal and non-gastrointestinal conditions. These observations have led to work demonstrating that an important mechanism of these agents is their close interaction with the gut associated lymphoid tissue (GALT) and suggested immunomodulatory effects on systemic immune response. Studies on the possibility that prebiotic agents might directly or indirectly induce similar immunomodulation have only recently begun. The preliminary findings of several recent human clinical trials reviewed in this article indicate that prebiotics may indeed prove to be a clinically beneficial dietary supplement, in the context of novel nutritional strategies for the management of gastrointestinal and systemic conditions.