Chemokines are small peptide mediators that play a role in many physiological and pathological processes. Apart from their initially discovered function in trafficking of leukocytes, they also influence migration, proliferation, survival and gene expression of a variety of cell types in their respective microenvironment. Chemokines can exert these effects via their respective G protein-coupled receptor. Over the recent decade, the involvement of chemokines and their respective receptors in tumor biology has been successively elucidated. This review will focus on the signaling and effects of the widespread chemokine CXCL12 and its long known G protein-coupled receptor CXCR4 and the recently discovered non-G protein-coupled receptor CXCR7 with a detailed reflection on glioma biology.