Lentiviruses consist of primate lentiviruses, ungulate lentiviruses and feline immunodeficiency virus (FIV). The primate lentiviruses utilize CD4 and chemokine receptors as a primary receptor and coreceptors, respectively. Recently we found that FIV utilizes CD134 and CXCR4 as a primary receptor and a coreceptor, respectively. FIV utilizes feline CD134 but not human CD134, whereas it can utilize both feline and human CXCR4. Exceptionally an FIV laboratory strain can infect human cells via CXCR4 only by the CD134-independent manner. Similarly several strains of primate lentiviruses also infect cells by the CD4-independent manner. In this review, the evolution of the lentiviruses and possible mechanism for lentiviral cross-species transmission is discussed.