Polyunsaturated fatty acids (PUFAs), which are known to be critical for human health, are lipids in which the constituent hydrocarbon chain possesses two or more carbon-carbon double bonds. PUFAs are distributed in almost all cells in the human body and affect membrane composition and function, eicosanoid synthesis, signal transduction, and gene expression. Linoleic acid (LA), an omega-6 fatty acid, and α- linolenic acid (ALA), an omega-3 fatty acid, are considered essential fatty acids because they cannot be synthesized by humans. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be synthesized from ALA; however, due to low conversion efficiency, EPA and DHA should be obtained from food sources. Foods that provide omega-3 fatty acids include fish oil and certain plant and nut oils, whereas omega-6 fatty acids can be found in palm, soybean, rapeseed, and sunflower oils. Omega-9 fatty acids, which are not considered essential, can be found in animal fat and olive oil. Fish oil contains two omega-3 fatty acids, i.e., DHA and EPA. Some nuts, seeds, and vegetable oils contain ALA, which may be converted into DHA and EPA in the body. Importantly, omega-6 PUFAs have been shown to promote inflammation and augment many diseases, whereas omega-3 PUFAs appear to counter these adverse effects. Indeed, omega-3 fatty acids are thought to provide a wide range of health benefits, including reducing the risk of coronary heart disease and improving cholesterol levels. Studies of omega-3 fatty acids have shown promising effects in cancer, diabetes mellitus, depression, and attention-deficit hyperactivity disorder. Due to these potential health benefits, fish oil, which is rich in omega-3 fatty acids, has become a popular supplement. Moreover, recommended amounts of DHA and EPA, consumed from fish or fish oil supplements, may lower triglycerides and reduce the risk of heart attack, arrhythmia, and stroke in individuals with heart disorders. To induce biological effects, PUFAs must be metabolized to their respective long-chain metabolites. PUFAs not only form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs) but also modify lipoxins (LXs), resolvins, and isoprostanes. Certain PGs, TXs, and LTs have pro-inflammatory effects, whereas LXs and resolvins are anti-inflammatory molecules. Furthermore, PUFAs and their long-chain metabolites modulate the activities of angiotensin-converting enzymes (ACE) and HMG-CoA reductase enzymes, enhance acetylcholine levels in the brain, increase the synthesis of endothelial nitric oxide, augment diuresis, and enhance insulin action. Thus, PUFAs and their metabolites may function as endogenous ACE and HMG-CoA reductase inhibitors, nitric oxide enhancers, β-blockers, diuretics, antihypertensive, and anti-atherosclerotic molecules. Additionally, PUFAs and their long-chain metabolites affect signal transduction via activation of peroxisome proliferator-activated receptors. Thus, PUFAs and their derivatives are involved in many physiological and pathological actions to regain homeostasis.