The plasma membrane of eukaryotic cells exhibits lateral inhomogeneities, mainly containing cholesterol and sphingomyelin, which provide liquid-ordered microdomains (lipid "rafts") that segregate membrane components. Rafts are thought to modulate the biological functions of molecules that become associated with them, and as such, they appear to be involved in a variety of processes, including signal transduction, membrane sorting, cell adhesion and pathogen entry. Although still a matter of ongoing debate, evidence in favor of the presence of these microdomains is gradually accumulating but a consensus on issues like their size, lifetime, composition, and biological significance has yet to be reached. Here, we provide an overview of the evidence supporting the presence of rafts in oligodendrocytes, the myelin-producing cells of the central nervous system, and discuss their functional significance. The myelin membrane differs fundamentally from the plasma membrane, both in lipid and protein composition. Moreover, since myelin membranes are unusually enriched in glycosphingolipids, questions concerning the biogenesis and functional relevance of microdomains thus appear of special interest in oligodendrocytes. The current picture of rafts in oligodendrocytes is mainly based on detergent methods. The robustness of such data is discussed and alternative methods that may provide complementary data are indicated.