Our findings demonstrate that (1) hypoxia upregulates CXCR7 protein expression in glioma cells, (2) CXCR7 mediates the migration of LN229 and LN308 glioma cells towards SDF-1α in hypoxic conditions, (3) SDF-1α induces CXCR7-mediated phosphorylation of ERK1/2 and Akt in LN229 and LN308 glioma cells, (4) inhibiting CXCR4 in glioma cells that are knocked down for CXCR7 does not further reduce either the migration towards SDF-1α or the levels of SDF-1α-induced phosphorylation of ERK1/2 and Akt, and (5) CXCR4 and CXCR7 bind in glioma cells. Here, CXCL12 is linked to central nervous system cancer.