An emerging concept in clinical nutrition is that dietary interventions may improve the course of systemic inflammatory disorders like rheumatoid arthritis and psoriasis. Most of this effect depends on the ability of polyunsaturated fatty acids (PUFAs) to modulate immune and inflammatory responses. Two main families of PUFAs exist in human tissues: n-3 PUFAs that have a marked anti-inflammatory activity and n-6 PUFAs that, conversely, promote inflammation. Multiple mechanisms account for the modulation of the inflammatory response by PUFAs. Recent lipidemic studies have added new mediators like lipoxins to the list of PUFA metabolites controlling inflammation that classically included only pro-inflammatory or anti-inflammatory prostaglandins like PGE2 and PGE3, respectively. The concerted activity of these mediators may determine a decreased recruitment of inflammatory cells in target tissues, with a lower release of pro-inflammatory cytokines like Interleukin-6 (IL-6) and necrosis tumor factor-α (TNF), and their higher apoptosis rate.