In the following review, we address difficulties that have arisen when attempting to convert the myelin multilayers into vesicles. The emphasis is on CNS myelin of adult mammals although both central nervous system (CNS) and peripheral nervous system (PNS) myelin are considered. The ability to prepare vesicle of myelin membrane has yet not been feasible. We hope to clarify some aspect of this problem and offer some possible approaches. Special attention is paid to myelin swelling phenomena because these indicate ways in which the myelin multilayer can break down. Images of isolated myelin are reviewed with special attention to the ways in which the multilayer actually breaks down. Attempts at reproducing a procedure for vesiculating myelin are summarized, and a critique is given to account for the inability to reproduce the published results. Finally, novel approaches for vesiculating myelin are proposed, which are based on well‐characterized swelling phenomena. © 1995 Wiley‐Liss, Inc.