Lipid mediators are a heterogenous group of bioactive lipids which includes eicosanoids, resolvins, endocannabinoids, sphingolipids, phospholipids and oxidized lipids. They mediate several physiological cellular functions but also participate in the pathogenesis of many diseases such as diabetes, cardiovascular diseases, autoimmune diseases and cancer. Many food-derived bioactive compounds can beneficially alter their metabolism or actions offering an attractive adjunct to the existing conventional therapies of the above diseases. Omega-3 fatty acids, polyphenols, phytosterols, vitamins and organosulfur compounds are potent modulators of lipid mediators biochemistry in vitro while an increased intake of foods, rich in the aforementioned ingredients, is related with a favorable clinical profile of many pathological conditions. Platelet activating factor (PAF) is one of the most potent inflammatory lipid mediators playing a crucial role in the initiation and propagation of atherosclerosis, therefore, the presence of PAF inhibitors in various foodstuffs is very important in terms of their nutritional value. Several dietary macronutrients and microconstituents, of plant origin mainly, are able to antagonize PAF actions and attenuate its effect in vivo. This article summarizes the effects of food ingredients on the metabolism and actions of lipid mediators. Special attention is given to the dietary modulation of PAF.