Eicosanoids, including epoxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and other oxylipins derived from polyunsaturated fatty acids, have emerging roles in endothelial inflammation and subsequent atherosclerosis. Unlike eicosanoids in the prostanoid series, they are known to be esterified in cell lipids such as phospholipids and triglycerides; however, our understanding of these reservoirs is in its infancy. This review focuses on recent work identifying circulating oxylipins, primarily esterified with lipoprotein lipids, and their effects on markers of endothelial dysfunction. These oxylipins are known to be released by at least one lipase (lipoprotein lipase) and to mediate increased expression of inflammatory markers in endothelial cells, which coincides with the known roles of lipoproteins in endothelial dysfunction. The implications of the lipolytic release of lipoprotein-bound oxylipins for the inflammatory response, challenges to analysis of this oxylipin compartment, and the potential importance of non-arachidonate-derived oxylipins are discussed.