Regenerative capacity is weak after central nervous system injury because of the absence of an enhancing microenvironment and presence of an inhibitory microenvironment for neuronal and axonal repair. In addition to the Nogo receptor (NgR), the paired immunoglobulin-like receptor B (PirB) is a recently discovered coreceptor of Nogo, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein. Concurrent blocking of NgR and PirB almost completely eliminates the inhibitory effect of myelin-associated inhibitory molecules on axonal regeneration. PirB participates in a key pathological process of the nervous system, specifically axonal regeneration inhibition. PirB is an inhibitory receptor similar to NgR, but their effects are not identical. This study summarizes the structure, distribution, relationship with common nervous system diseases, and known mechanisms of PirB, and concludes that PirB is also distributed in cells of the immune and hematopoietic systems. Further investigations are needed to determine if immunomodulation and blood cell migration involve inhibition of axonal regeneration. © 2015, Editorial Board of Neural Regeneration Research. All rights reserved.