CXCR4 was found to be expressed by many different types of human cancers and its expression has been correlated with tumor aggressiveness, poor prognosis and resistance to chemotherapy. CXCR4 was also shown to contribute to metastatic seeding of organs that express its ligand CXCL12 and support the survival of these cells. These findings suggest that CXCR4 is a potentially attractive therapeutic target, and several antagonists and antibodies for this receptor were developed and are under clinical evaluation. Quantifying CXCR4 expression non-invasively might aid in prognostication as a mean for personalized therapy and post treatment monitoring. Multiple attempts were done over the recent years to develop imaging agents for CXCR4 using different technologies including PET, SPECT, fluorescent and bioluminescence, and will be reviewed in this paper.