The mammalian nervous system is relatively autonomous in lipid metabolism. In particular, Schwann cells in the peripheral nervous system, and oligodendrocytes and astrocytes in the central nervous system, are highly active in lipid synthesis. Previously, enzymatic lipid synthesis in the liver has been demonstrated to be under the control of the sterol regulatory element-binding protein (SREBP) transcription factors. Here, we put forward the view that SREBP transcription factors in glia cells control the synthesis of lipids involved in various glia-neuron interactions, thereby affecting a range of neuronal functions. This minireview compiles current knowledge on the involvement of Schwann cell SREBPs in myelination of axons in the peripheral nervous system, and proposes a role for astrocyte SREBPs in neuronal functioning in the central nervous system. © 2008 FEBS.