EPA and DHA are the main omega-3 PUFAs present in oily fish and fish supplements, and also other marine sources. Omega-3 PUFAs can be enzymatically transformed into various bioactive autacoids that have a potent modulating effect on inflammation, especially resolution phase of inflammation. Their role is described in rodents and humans. The fatty acid composition in the membrane changes membrane fluidity, signaling through the membrane, leading to a change in gene expression, also influencing composition of lipid mediator molecules, and modulated lipid raft formation. The cells involved in the inflammatory response are typically rich in omega-6 AA, but that composition may change. Eicosanoids produced with AA such as PGE2 and 4-series LT have proinflammatory properties, their similar EPA analogs being less potent. Also, EPA and DHA create resolvins protectins, maresins with anti-inflammatory and proresorptive capability. Improper and uncontrolled inflammation leads to a spectrum of human illnesses. In physiological conditions it is believed that there will be a balance between the pro and anti-inflammatory molecules. When the balance is disturbed we will have suppression or exacerbation of inflammation. Thus, it is necessary to maintain the balance of these bioactive lipids from various sources of PUFA for our health. There is significant evidence that these fatty acids can interfere and partially inhibit many inflammatory processes such as leukocyte chemotaxis, expression of adhesion molecules, leukocyte and endothelial interaction, production of eicosanoids such as PG and LT from omega-6 AA, and production of cytokines such as TNF-L and IL-1B. EPA and DHA operate across multiple mechanisms of action. Further understanding of the pathways of omega-3 PUFA in health and disease may lead to the development of effective therapeutic strategies for the treatment of chronic inflammatory diseases.