Neuroinflammation characterizes various neurological disorders. Peripheral immune cells and CNS-resident glia contribute to neuroinflammation and impact CNS degeneration, recovery and regeneration. Recently, the role of dendritic cells in neuroinflammation received special attention. The function of infiltrating immune cells and resident glia is affected by various factors, including lipid mediators. Polyunsaturated fatty acids, especially n-6 arachidonic acid and n-3 docosahexaenoic acid (DHA), the most abundant in the CNS, play an important role in neuroinflammation. The major arachidonic acid bioactive derivative in immune cells, PGE2, and DHA have been reported to have opposite effects on dendritic cells in terms of cytokine production and activation/differentiation of CD4(+) T cells. Here we review the existing information on PGE2 and DHA modulation of dendritic cell function and the potential impact of these lipid mediators of dendritic cells in CNS inflammatory disorders.