Flavonoids are polyphenolic substances derived from plants that play several pharmacological activities. They possess anti-viral, anti-microbial, anti-inflammatory and anti-allergic potential that can be expressed on different cell types, both in animal and human models. Many of these properties prove inhibitory to a huge panoply of molecular targets in the micromolar concentration range, either by down-regulating or suppressing many inflammatory pathways and functions. Flavonoids exert their properties both as purified aglycone molecules and as plant extracts. Depending on little changes in the flavone-backbone and on subtle mechanisms of cell behavior and responsiveness, flavonoids can play a modulating, biphasic and regulatory action on immunity and inflammation; in this context only few flavones and flavonols have been assayed, mainly because of their chemical similarity with quercetin, so evidence reported in the literature about the action of flavonoids is limited to a restricted group of molecules. Many of the effects reported about flavonoids regard quercetin, as probably the most diffused and known nature-derived flavonol. Quercetin has shown a biphasic behavior in basophils at nanomolar doses and hence its action on cells involved in allergic inflammation is here described. Like many other molecules sharing a flavone ring, quercetin affects immunity and inflammation by acting mainly on leukocytes and targeting many intracellular signaling kinases and phosphatases, enzymes and membrane proteins often crucial for a cellular specific function. This overview collects and discusses the role of flavonoids as anti-infectious and anti-inflammatory compounds, trying to focus on the complex and modulating interaction of these polyphenolic substances with cell function. However, the wide group of intracellular targets and the elevated number of natural compounds potentially effective as anti-inflammatory therapeutical agents, asks for further insights and evidence to comprehend the role of these substances in animal cell biology.