Inflammation is a defensive response to injury and infection, but excessive or inappropriate inflammation contributes to a range of acute and chronic human diseases. Clinical assessment of dietary supplementation of omega-3 polyunsaturated fatty acids (PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) indicate their beneficial impact on human diseases in which inflammation is suspected as a key component of the pathogenesis. Although the mechanism of EPA and DHA action is still not fully defined in molecular terms, recent studies have revealed that, during the course of acute inflammation, omega-3 PUFA-derived mediators including resolvins and protectins with potent anti-inflammatory and pro-resolving properties are produced. In this review, we provide an overview of the formation and actions of EPA-derived anti-inflammatory lipid mediator resolvin E1.