Development of myelinating glia and the myelination process both require dramatic changes in the pattern of gene expression. During these processes, cells of the oligodendrocyte and Schwann cell lineages have to alter the transcription rates of numerous genes in a highly coordinated manner. This is made possible by the combined action of a set of transcription factors with preferential expression in these cells. Recent years have seen the identification of such glial transcription factors, including several homeodomain proteins, zinc finger proteins and HMG-domain proteins. Understanding their mode of action will help to unravel the molecular basis of myelination and will provide insights into the causes of myelinopathies and related diseases.