Lipid peroxidation was mechanistically revealed in the 1940s thanks to the scientists at the British Rubber Products Association, and only then, the role of free radicals derived from molecular oxygen started to make sense leading to the understanding of the autooxidation phenomena . Soon enough, the discovery of arachidonic acid (AA) cascade (enzyme-catalyzed peroxidation) led to the discovery of bioactive eicosanoids, and oxylipins produced by other polyunsaturated fatty acids (PUFA) than AA. Finally, non-enzymatic oxygenated metabolites of polyunsaturated fatty acids (NEO-PUFAs) were originally identified as mere product of oxidative stress (hence potential biomarkers), however several evidences highlighted their role as lipid mediators like the isoprostanoids . Early methods for detection and quantification of oxylipins in samples relied on thin-layer chromatography (TLC), gas chromatography (GC), and mass spectrometry (MS). Over the past three decades, advances in hyphenated techniques such as liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) along with high resolution MS and novel data analysis approaches have allowed the comprehensive analysis of the various modifications of lipids by enzymatic and non-enzymatic reactions, forming higher levels of structural complexity, known as the epilipidome . One of the challenges in epilipidomics is the identification of the modified lipids, especially so if they were already discovered, i.e., the dereplication of oxidized lipids .