Dietary flavonoids have been reported to possess a wide range of activities in the prevention of common diseases, and recent evidence suggests that they possess immunomodulatory and anti-inflammatory properties. Effects appear to be related to the various biological/pharmacological activities of flavonoids. However, almost all studies are in vitro studies with limited research on animal models and scarce data from human studies. The majority of in vitro research has been carried out with single flavonoids, generally aglycones, at rather supraphysiological concentrations. Few studies have investigated the anti-inflammatory effects of physiologically attainable flavonoid concentrations in healthy subjects, and more epidemiological studies and prospective randomized trials are still required. This chapter highlights the evidence for the effects of flavonoids in inflammation and immunity. Mechanisms are discussed, including those on enzyme function and regulation of gene and protein expression. Animal work is included and evidence from epidemiological studies and human intervention trials is reviewed.