Fatty acids with greater than 22 carbon atoms (very long chain fatty acids, VLCFA) are present in small amounts in most animal tissues. Saturated and monoenoic VLCFA are major components of brain, while the polyenoic VLCFA occur in significant amounts in certain specialized animal tissues such as retina and spermatozoa. Biosynthesis of VLCFA occurs by carbon chain elongation of shorter chain fatty acid precursors while beta-oxidation takes place almost exclusively in peroxisomes. Mitochondria are unable to oxidize VLCFA because they lack a specific VLCFA coenzyme A synthetase, the first enzyme in the beta-oxidation pathway. VLCFA accumulate in the tissues of patients with inherited abnormalities in peroxisomal assembly, and also in individuals with defects in enzymes catalyzing individual reactions along the beta-oxidation pathway. It is believed that the accumulation of VLCFA in patient tissues contributes to the severe pathological changes which are a feature of these conditions. However, little is known of the role of VLCFA in normal cellular processes, and of the molecular basis for their contribution to the disease process. The present review provides an outline of the current knowledge of VLCFA including their biosynthesis, degradation, possible function and involvement in human disease.