CCR5, as the member of CC receptor family, with its ligands being CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES), is categorized as 7 transmembrane domain G-protein coupled receptor. CCR5 is expressed in monocytes/macrophages as well as lymphocytes inducing chemotaxis and recruitment in inflammatory response and is an important co-receptor of human immunodeficiency virus (HIV)-1 virus, leading to the multifunction of CCR5 in progression of various kind of immunological diseases and invasion of HIV-1. Moreover, the expression of CCR5 on the surface of tumor cells and stromal cells contributes to mediating multiple biological behaviors of cancers such as proliferation and invasion. Advanced technologies also lead to the revealing of structure, function, signal transduction and roles of CCR5 in the progression of related diseases.