Essential dietary fatty acids (18:2,n-6 and 18:3,n-3) are converted to arachidonic acid (20:4,n-6) and docosahexaenoic acid (22:6,n-3) by a series of desaturation (fatty acid desaturases, Δ5D[FADS1] & Δ6D[FADS2]), elongation (fatty acid elongases, Elovl2 & Elovl5), and peroxisomal β-oxidation (pβ-Ox) steps. Peroxisomal retroconversion of 22:6,n-3 to 20:5,n-3 is illustrated by the strippled line. The boxed fatty acids, 18:2,n-6, 20:4,n-6, and 22:6,n-3, are the predominant PUFA appearing in hepatic membrane lipids. The recently described alternative route involving 20:2,n-6 as an intermediate for 20:3,n-6 and 20:4,n-3 synthesis is illustrated (238). Several of these fatty acids are precursors to pro- (red) and anti-inflammatory (green) eicosanoids and docosanoids (239, 240).