© 2015 Informa UK, Ltd. HIV-1 is the most prevalent retrovirus, with over 30 million people infected worldwide. Nevertheless, infection caused by other human retroviruses like HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4 is gaining importance. Initially confined to specific geographical areas, HIV-2, HTLV-1 and HTLV-2 are becoming a major concern in non-endemic countries due to international migration flows. Clinical manifestations of retroviruses range from asymptomatic carriers to life-threatening conditions, such as AIDS in HIV-2 infection or adult T-cell lymphoma/leukemia or tropical spastic paraparesis in HTLV-1 infection. HIV-2 is naturally resistant to some antiretrovirals frequently used to treat HIV-1 infection, but it does have effective antiretroviral therapy options. Unfortunately, HTLV still has limited therapeutic options. In this article, we will review the epidemiological, clinical, diagnostic, pathogenic and therapeutic aspects of infections caused by these human retroviruses.