Fructans are natural fructose polymers that are used for their prebiotic and health improving properties in functional foods. Although the immunomodulatory effects of fructans on animal cells are known, their mode of action has only recently been unraveled. It was found that inulin-type fructans act as signals in animals, stimulating immune cell activity through Toll Like Receptor (TLR)° mediated signaling. This review summarizes recent progress in the area with focus on possible fructan signaling and downstream signaling events. Intriguingly, synergistic effects with phenolic compounds are often observed. Fructans and their fermentation products (short chain fatty acids and hydrogen gas) lead to a more reduced cellular status and a modulation of the immune system, aiming at disease prevention. Moreover, evidence is accumulating that fructans may alleviate inflammatory symptoms in diseased subjects. In conclusion, fructans are of interest in functional foods because of their prebiotic, antioxidant and immunomodulatory properties.