The neurotrophin receptor p75(NTR) has long been known as a receptor for neurotrophins that promote survival and differentiation. Consistent with the role of neurotrophins, p75(NTR) is expressed during the developmental stages of the nervous system. However, p75(NTR) is re-expressed in various pathological conditions in the adult. We now know that p75(NTR) has the ability to elicit bi-directional signals, that result in the inhibition as well as the promotion of the neurite outgrowth. p75(NTR) is a key receptor for myelin-derived inhibitory cues that contribute to the lack of regeneration of the central nervous system.