The myelin membrane comprises a plethora of regions that are compositionally, ultrastructurally, and functionally distinct. Biochemical dissection of oligodendrocytes, Schwann cells, and central and peripheral nervous system myelin by means such as cold-detergent extraction and differential fractionation has led to the identification of a variety of detergent-resistant membrane assemblies, some of which represent putative signalling platforms. We review here the different microdomains that have hitherto been identified in the myelin membrane, particularly lipid rafts, caveolae, and cellular junctions such as the tight junctions that are found in the radial component of the CNS myelin sheath.