2018 by Taylor & Francis Group, LLC. T-cell-mediated high-grade and low-grade chronic inammatory diseases, including obesity and its associated metabolic syndrome, are a global health problem [1-3]. Although pharmaceuticals such as nonsteroidal anti-inammatory drugs (NSAIDs) and glucocorticoids are available for treatment of high-grade inammation, they are expensive and often trigger serious side effects [4,5]. Given the high proportion of the population that is aficted by chronic inammation, it is important to identify innocuous anti-inammatory dietary compounds that could ameliorate inammation and improve overall health in the population. Mounting evidence suggests that n-3 polyunsaturated fatty acids (PUFAs), found in oily sh and sh oil supplements, offer great potential as anti-inammatory agents or as adjunctive therapies with established drugs [6-18]. The primary bioactive n-3 PUFAs are thought to be eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), which have been shown to attenuate inammatory responses, biomarkers, and mortality in preclinical models [19-22] and humans [6-17]. From an immunological perspective, the anti-inammatory properties of EPA and DHA include effects on mediators of both the innate immune response [23-26] and the adaptive immune response. In this chapter, we will review the anti-inammatory and immunomodulatory mechanisms by which n-3 PUFAs inuence T-cell responses.