Impaired axonal regeneration is a common observation after central nervous system (CNS) injury. The stromal cell-derived factor-1, SDF-1/CXCL12, has previously been shown to promote axonal growth in the presence of potent chemorepellent molecules known to be important in nervous system development. Here, we report that treatment with SDF-1alpha is sufficient to overcome neurite outgrowth inhibition mediated by CNS myelin towards cultured postnatal dorsal root ganglion neurons. While we found both cognate SDF-1 receptors, CXCR4 and CXCR7/RDC1, to be coexpressed on myelin-sensitive dorsal root ganglion neurons, the distinct expression pattern of CXCR4 on growth cones and branching points of neurites suggests a function of this receptor in chemokine-mediated growth promotion and/or arborization. These in vitro findings were further corroborated as local intrathecal infusion of SDF-1 into spinal cord injury following thoracic dorsal hemisection resulted in enhanced sprouting of corticospinal tract axons into white and grey matter. Our findings indicate that SDF-1 receptor activation might constitute a novel therapeutic approach to promote axonal growth in the injured CNS.