Cells of macrophage lineage contribute to the pathogenesis of HIV-1 infection throughout the course of disease. Blood monocytes and tissue macrophages can be infected with HIV-1 in vivo and in vitro. In contrast to tissue macrophages, which are highly susceptible to HIV-1 infection, blood monocytes are relatively resistant to HIV-1, with the possible exception of their CD14lo / CD16hi subset. Cells of macrophage lineage can be infected mainly with macrophage (M)-tropic strains, although infection with some T cell line (T)-tropic strains or dual-tropic isolates of HIV-1 also occurs. Following HIV-1 infection, monocyte / macrophages are resistant to cytopathic effects of the virus. The assembly of HIV-1 in macrophage subcellular vesicles rather than budding from the plasma membrane may help to preserve long-term cell viability. Macrophages can therefore persist throughout the course of infection as long-term stable reservoirs for HIV-1 capable of disseminating the virus to tissues. These cells contribute to the development of HIV-induced dementia via production of proinflammatory cytokines and neurotoxins. Following HIV-1 infection, monocyte / macrophages also display impaired effector functions such as phagocytosis, intracellular killing and cytokine production, contributing to the development of opportunistic infections. This review provides insights into the most recent studies on the role of monocyte / macrophages in the pathogenesis of HIV-1 infection by serving as viral targets and reservoirs, contributing to neuropathogenesis and opportunistic infections.