Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are biologically active. The main biologically active n-6 PUFA is arachidonic acid. Most cell membranes contain fairly high amounts of arachidonic acid within different phospholipids. The arachidonic acid is mobilised by phospholipase enzymes upon cellular stimulation and the free arachidonic acid is itself a signalling molecule whilst also acting as the primary substrate for synthesis of the eicosanoid family of lipid mediators. These are produced through various pathways notably those involving cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. The mediators produced have diverse roles in regulating inflammation, immunity, smooth muscle contraction, platelet function, blood clotting etc. The major biologically active n-3 PUFAs are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Both these fatty acids are readily incorporated into cell membranes where they partially replace arachidonic acid. They also inhibit arachidonic acid metabolism so reducing the production of the principal families of eicosanoids. However EPA and DHA are themselves precursors for synthesis of lipid mediators. Eicosanoids produced from EPA are typically biologically weak, while resolvins produced from EPA and DHA and protectins produced from DHA seem to be very potent inflammation resolving agents. PUFAs and PUFA-derived lipid mediators appear to be ligands for peroxisome proliferator activated receptors and through this mechanism may alter lipid metabolism, insulin sensitivity, adipocyte development and inflammation. Incorporating EPA and DHA into cell membranes can disrupt formation of lipid rafts so modulating the early stages of signal transduction. Theoretically a higher PUFA content of cell membranes alters membrane order which may impact on protein movement and signalling mechanisms. Through the actions of PUFAs on membranes, on signalling, and on intracellular sensors they can alter patterns of gene expression and protein production. Thus, the nature of the PUFAs to which cells are exposed influences their function and their ability to respond to signals.