The degradation of fatty acids (FAs) via beta-oxidation involves successive rounds of four reactions that remove two carbons from the FA acyl chain per cycle as acetyl-CoA. Beta-oxidation of very long-chain and branched FAs occurs in the peroxisome and requires prior ligation of the FA to CoA (activation). The peroxisomal break-down of FAs is usually incomplete, generating short-, medium-, and long-chain FAs that are transferred to the mitochondrion for complete degradation. Three auxiliary enzymes, delta(3)-delta(2)-enoyl-CoA isomerase, delta(3,5)-delta(2,4)-dienoyl-CoA isomerase and 2,4-dienoyl-CoA reductase, converts the double bonds in mono- and polyunsaturated FAs that are not recognized by the core cycle enzymes, to the 2-trans-enoyl-CoA configuration allowing re-entry into the beta-oxidation cycle. (Adapted from FBrf0219445.)