Human immunodeficiency virus (HIV) remains a significant source of morbidity and mortality worldwide. No effective vaccine is available to prevent HIV transmission, and although antiretroviral therapy can prevent disease progression, it does not cure HIV infection. Substantial effort is therefore currently directed toward basic research on HIV pathogenesis and persistence and developing methods to stop the spread of the HIV epidemic and cure those individuals already infected with HIV. Humanized mice are versatile tools for the study of HIV and its interaction with the human immune system. These models generally consist of immunodeficient mice transplanted with human cells or reconstituted with a near-complete human immune system. Here, we describe the major humanized mouse models currently in use, and some recent advances that have been made in HIV research/therapeutics using these models.