Growth factor-activated and cell adhesion-mediated signaling plays a crucial role in the development and differentiation of oligodendrocytes and astrocytes, the two macroglial cells of the CNS. Guided by the recent advances in the elucidation of intracellular signaling pathways, researchers have begun to investigate the mechanisms that regulate gliogenesis, glial cell differentiation and myelinogenesis. The progress made so far strongly implicates protein kinase C (PKC)- and protein kinase A (PKA)-mediated signaling in glial cell proliferation and differentiation. These pathways are also involved in the morphogenesis of astrocytes and in the myelin gene expression of oligodendrocytes. The cellular responses elicited by both PKC and PKA pathways in oligodendrocytes are developmentally controlled. The PKC pathway also seems to play a key role in phenotypic plasticity and regeneration of oligodendrocytes. Initial events of myelination requiring cell surface interactions may involve signaling via Fyn kinase which functionally associates with myelin-associated glycoprotein, an adhesion molecule implicated in myelinogenesis.