Fatty acids (FA) are involved in both physiologic and pathologic biochemical pathways. Saturated FA (mainly 12-C and 14-C) are implicated in the development of hypercholesterolemia and early atherogenesis. On the contrary, monounsaturated and polyunsaturated FA (mainly 18:2 n-6 and n-3 very long-chain FA) have been claimed to have hypocholesterolemic and protective effects. In particular, oleic acid (18:1 n-9) seems to lower only the atherogenic fraction of circulating cholesterol (the low-density lipoproteins), leaving immodified the level of the protective fraction (the high-density lipoproteins). Polyunsaturated very long-chain FA have been recently studied for the prevention and therapy of atopic and cutaneous disorders, with conflicting results. In this respect, the 20:4 n-6 acts as proinflammatory agent, while the n-3 very long-chain FA could act as modulators of the immuno-allergic and inflammatory reactions. However, attention must be paid to the high peroxidative potential of the more unsaturated FA. Very recently, VLCFA have been considered for the therapy of some inherited disorders of metabolism. Monounsaturated very long-chain FA have been used in the treatment of x-linked adrenoleukodystrophy. A dietetic deficiency of polyunsaturated very long-chain FA has been observed in treated phenylketonuric children. Some inborn errors of metabolism could represent an useful model for better understanding the biochemistry of FA.