Oligodendrocytes have a high rate of synthetic activity and produce vast amounts of myelin. The membrane production requires specific sorting and transport processes and structural support. In culture, oligodendrocytes extend flat membranous sheets containing an extensive cytoskeletal network of microtubules (MTs) and microfilaments (MFs). The microtubules participate in the elaboration and stabilization of the myelin-containing cellular processes and have an impact not only on the complex oligodendroglia architecture but also influence their functions. They participate in intracellular sorting processes and the translocation of myelin basic protein (MBP) mRNAs to the forming myelin sheath. The two major groups of neuronal microtubule-associated proteins (MAPs), MAP2 and tau are expressed in oligodendrocytes and might be involved in the regulation of MT stability and organization. Myelin-specific proteins, such as MBP and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), interact with the cytoskeleton. Glial changes occur in a variety of neurodegenerative diseases, and glial fibrillary tangles and glial cytoplasmic inclusions (GCIs), containing abnormal microtubular structures which stain positively for stress proteins and microtubule-associated proteins, are found in oligodendrocytes of the affected brains. The role of MTs and their associated proteins in oligodendrocytes during normal development and pathological situtations is specifically emphasized in this review.