Studies of animals fed diets with different proportions of polyunsaturated fatty acids (PUFAs) have identified dietary requirements for maintaining optimal brain function and membrane PUFA composition. In addition, these studies have shown that metabolic, functional and behavioral changes can arise from long-term n-3 PUFA dietary deprivation. Clinical studies also have revealed that a low dietary consumption of n-3 PUFAs or a low plasma docosahexaenoic acid (DHA, 22:6n-3) concentration is correlated with a number of brain diseases, and with cognitive or behavioral defects during early development and aging. Most of the DHA accumulates in the brain during the perinatal period (development and lactation). Sufficient evidence is available to conclude that maternal fatty acid nutrition is important to DHA transfer to the infant before and after birth, with short and long-term implications for neural function. Although the molecular mechanism of DHA remains unclear, more and more data demonstrate its role in various cellular activities contributing to regulation of neuronal functions. As fundamental components of membrane phospholipids, PUFAs modulate activity of enzymes, transporters and receptors. They also are precursors of lipid mediators involved in signaling pathways and neuroinflammatory processes. As natural ligands of nuclear receptors, they participate in regulation of numerous genes, implicated in lipid and glucose metabolism.