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Antiretroviral therapy (ART) controls viral replication and has dramatically improved the quality of life and life expectancy of people living with HIV (PLHIV). However, almost forty years after the discovery of HIV, there is still no cure; even after years of effective ART, the virus persists in cells, primarily memory CD4 T cells. These cells are a perennial source of infectious viruses, which require people living with HIV to continue ART for life. Research on HIV reservoirs over the past twenty-five years has provided insight into how some infected cells persist for decades without being cleared by ART or by immune responses. HIV “hides” in cells with extended lifespans, which have the capacity to proliferate through diverse mechanisms and which preferentially express several receptors that allow them to remain invisible to the immune system. A better understanding of these mechanisms of persistence is a necessary pre-requisite for the development of therapeutic strategies aimed at eradicating HIV.