Inflammation is part of the normal host response to infection and injury. However, excessive or inappropriate inflammation contributes to a range of acute and chronic human diseases and is characterized by the production of inflammatory cytokines, arachidonic acid–derived eicosanoids (prostaglandins, thromboxanes, leukotrienes, and other oxidized derivatives), other inflammatory agents (eg, reactive oxygen species), and adhesion molecules. At sufficiently high intakes, long-chain n−3 polyunsaturated fatty acids (PUFAs), as found in oily fish and fish oils, decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species and the expression of adhesion molecules. Long-chain n−3 PUFAs act both directly (eg, by replacing arachidonic acid as an eicosanoid substrate and inhibiting arachidonic acid metabolism) and indirectly (eg, by altering the expression of inflammatory genes through effects on transcription factor activation). Long-chain n−3 PUFAs also give rise to a family of antiinflammatory mediators termed resolvins. Thus, n−3 PUFAs are potentially potent antiinflammatory agents. As such, they may be of therapeutic use in a variety of acute and chronic inflammatory settings. Evidence of their clinical efficacy is reasonably strong in some settings (eg, in rheumatoid arthritis) but is weak in others (eg, in inflammatory bowel diseases and asthma). More, better designed, and larger trials are required to assess the therapeutic potential of long-chain n−3 PUFAs in inflammatory diseases. The precursor n−3 PUFA α-linolenic acid does not appear to exert antiinflammatory effects at achievable intakes.