The wrapping of multiple layers of myelin membrane sheets around an axon is of fundamental importance for the function of the nervous system. In the central nervous system (CNS) oligodendrocytes synthesize tremendous amounts of cellular membrane to form multiple myelin internodes of highly stable membranes with a specific set of tightly packed lipids and proteins. In recent years, mouse mutants have allowed great advances in our understanding of the functional and structural role of many of the major components of myelin. The challenge now is to extend this knowledge to unravel the molecular machinery and mechanisms required to synthesize, assemble and wrap myelin multiple times around an axon at the appropriate developmental time. Such insight will be essential in designing new therapeutic strategies to promote remyelination in demyelinating disorders such as multiple sclerosis.