The innate immune system of the brain is principally composed of microglial cells and astrocytes, which, once activated, protect neurons against noxious agents or lesions. Activated glial cells produce inflammatory cytokines that act specifically through receptors expressed in the brain, leading to the development of altered emotional and cognitive behavior. These behavioral alterations cease along with the synthesis of brain cytokines. When the level of expression of these cytokines remains high, they become toxic to neurons possibly leading to neuronal death, as observed in neurodegenerative disorders such as Alzheimer’s disease. Omega-3 (n-3) type polyunsaturated fatty acids (PUFAs) are essential nutrients and fundamental components of neuronal and glial cell membranes. Additionally, they have immunomodulatory properties. They accumulate in the brain during the perinatal period in a dietary supply-dependant fashion. Their brain levels diminish with age, but can be corrected by a diet enriched in n-3 PUFAs. The increasing exposure of the population to diets unbalanced in n-3 PUFAs could contribute to the deleterious effect of inflammatory cytokines in the brain.