Brain is highly enriched in long-chain polyunsaturated fatty acids (PUFAs), particularly arachidonic acid and docosahexaenoic acid, which play important roles in brain structural and biologic functions. Plasma transport, in the form of free fatty acids or esterified FAs in lysophosphatidylcholine and lipoproteins, and de-novo synthesis contribute to brain accretion of long-chain PUFAs. Transport of long-chain PUFAs from plasma may play important roles because of the limited ability of brain to synthesize long-chain PUFAs, in the face of high demand for them. Although several proteins involved in facilitated fatty acid transport (e.g. fatty acid transport protein, fatty acid binding protein and very-long-chain acyl-coenzyme A synthetase) have been found in brain, their roles in fatty acid accumulation in brain are poorly defined. The primary pathways that are involved in long-chain PUFA accumulation in brain may vary according to brain region and developmental stage.