This chapter outlines some of the various components which may contribute to the observed lack of regeneration which occurs after injury to the adult mammalian central nervous system (CNS). To date, three major inhibitors of axonal regeneration associated with myelin have been identified: myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte-myelin glycoprotein (OMgp). The myelin-associated inhibitors all appear to be present in undamaged myelin and may have roles other than the block of regeneration or inadvertent sprouting. Following the binding of each of the myelin-associated inhibitors to the NgR-p75NTR-LINGO receptor complex, there is an induction of a signaling pathway which eventually leads to the blockage of neurite extension from damaged or naïve adult neurons. If the binding or signaling of a single receptor complex can be compromised, it may be possible to permit sufficient regeneration in the adult mammalian CNS after injury, particularly prior to formation of the glial scar.