Myelin sheaths include an extraordinary structure, the “paranodal axoglial junction” (PNJ), which attaches the sheath to the axon at each end of each myelin segment. Its size is enormous and its structure unique. Here we review past and current studies showing that this junction can serve multiple functions in maintaining reliable saltatory conduction. The present evidence points to three functions in particular. 1) It seals the myelin sheath to the axon to prevent major shunting of nodal action currents beneath the myelin sheath while still leaving a narrow channel interconnecting the internodal periaxonal space with the perinodal space. This pathway represents a potential route through which juxtaparanodal and internodal channels can influence nodal activity and through which nutrients, such as glucose, and other metabolites can diffuse to and from the internodal periaxonal space. 2) It serves as a mechanism for maintaining discrete, differentiated axolemmal domains at and around the node of Ranvier by acting as a barrier to the lateral movement of ion channel complexes within the axolemma, thus concentrating voltage-gated sodium channels at the node and segregating fast voltage-gated potassium channels to the juxtaparanode under the myelin sheath. 3) It attaches the myelin sheath to the axon on either side of the node and can thus maintain nodal dimensions in the face of mechanical stresses associated with stretch or other local factors that might cause disjunction. It is therefore the likely means for maintaining constancy of nodal surface area and electrical parameters essential for consistency in conduction. © 2009 Wiley-Liss, Inc.