The article reviews the critical roles of macrophages in HIV-1 infection and pathogenesis. Initially, macrophages were recognized as target cells for HIV-1, but their specific roles were largely overlooked. Recent studies have shown that macrophages play important direct and indirect roles in all stages of HIV-1 pathogenesis, including virus transmission, dissemination, and persistence. Infected macrophages are found in various tissues of HIV-1-infected patients, often as multinucleated giant cells expressing viral antigens, and can persist for long periods. Macrophages also participate in chronic inflammation and associated clinical disorders, even in patients on effective antiretroviral therapy (cART). The review discusses the presence, roles, and consequences of infected macrophages in different tissues, the specificities of virus replication and restriction in macrophages, and the role of macrophages in chronic immune activation and inflammation. It highlights the importance of macrophages in HIV-1 pathogenesis and the need for further research to understand their complex roles.The article reviews the critical roles of macrophages in HIV-1 infection and pathogenesis. Initially, macrophages were recognized as target cells for HIV-1, but their specific roles were largely overlooked. Recent studies have shown that macrophages play important direct and indirect roles in all stages of HIV-1 pathogenesis, including virus transmission, dissemination, and persistence. Infected macrophages are found in various tissues of HIV-1-infected patients, often as multinucleated giant cells expressing viral antigens, and can persist for long periods. Macrophages also participate in chronic inflammation and associated clinical disorders, even in patients on effective antiretroviral therapy (cART). The review discusses the presence, roles, and consequences of infected macrophages in different tissues, the specificities of virus replication and restriction in macrophages, and the role of macrophages in chronic immune activation and inflammation. It highlights the importance of macrophages in HIV-1 pathogenesis and the need for further research to understand their complex roles.