Docosahexaenoic acid (DHA, C22: 6n-3) is the most abundant polyunsaturated fatty acid in neuronal phospholipids, particularly in the cortex. The main source of DHA for neural cells is food, and hepatic and astroglia DHA synthesis from essential a-linolenic acid (C18: 3n-3). Accretion of DHA in the brain is most intensive during fetal life and the first two years of life. An adequate level of DHA in cell membranes is important for many functions of neural cells and this is presumably the reason for DHA saving in the adult mammalian brain during dietary a-linolenic acid deficiency. DHA-containing phospholipids in membranes are flexible and membranes possessing a high content of them are quite thin, more permeable to ions and small molecules, have looser lipid packing, and finally are more "dynamic" than membranes composed of other fatty acid containing phospholipids. Furthermore, these membranes create an appropriate environment for integral proteins highly condensed in neurons, such as receptors, ion channels, enzymes, and peripheral proteins. The quantity of phosphatidylserine in the inner membrane lipid layer depends on the availability of DHA to neurons. Phosphatidylserine promotes neuronal survival by translocation/activation of kinase Akt and Raf-1/MEK. DHA present in membrane phospholipids facilitates v-SNARE/t-SNARE complex formation, which is necessary for fusion of synaptic vesicles and plasma membranes necessary for transmitter exocytosis, and neurite outgrowth-dependent plasticity. DHA plays an important neuroprotective role. DHA has been shown to inhibit PGE2 synthesis and COX-1 expression in astrocytes, and DHA derivatives, especially neuroprotectins D, can suppress inflammatory responses, preventing neuronal damage or apoptosis. The results of high DHA content in neuronal membranes and formation of DHA derivates, as well as the function of DHA-dependent phosphatidylserine, may explain the promising results supporting beneficial DHA supplementation in neurodegenerative diseases and improvement of brain function.