Human immunodeficiency virus type 1 (HIV-1), which is the causative agent of acquired immunodeficiency syndrome, is a human-specific virus. Because HIV-1 cannot infect and cause disorders in other animals, it has been an arduous struggle to study the dynamics of HIV-1 infection in vivo. To understand and elucidate HIV-1 pathogenesis in vivo, several small animal models for HIV-1 infection have been established and improved over the last 20 years. Recently, a novel murine model, 'humanized mouse', has been generated. A humanized mouse has the potential to maintain human hematopoiesis including human CD4(+) leukocytes and, therefore, is able to support persistent HIV-1 infection in vivo. We herein describe the current state-of-the-art in HIV-1-infected humanized mice and introduce insights and perspectives of their use for HIV-1 studies in vivo.