Mechanistic insights on the trafficking of NOTCH-dependent leukemia cells to target organs are still ill-defined, however, recent reports have highlighted the importance of some homing receptors and their ligands (Figure 1) such as: (i) CC-chemokine ligand 19 (CCL19)/CC-chemokine receptor 7 (CCR7) (21); (ii) CXC-chemokine ligand 12 (CXCL12)/CXC-chemokine receptor 4 (CXCR4) (22–24); and (iii) CCL25/CCR9 (25). The gene discussed is CXCR4; the disease is leukemia.