– C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. This receptor is one of several chemokine receptors that HIV isolates can use to infect CD4+ T cells. CXCR4 stands out for its pleiotropic roles in both physiological and pathological conditions and it represents a crucial target in drug development. CXCL12 is the principal CXCR4 specific ligand and that the pro-inflammatory chemokine macrophage migration inhibitory factor (MIF) is also able to bind and activate CXCR4.