As described above, monocytes/macrophages from such diverse areas as the CNS, lungs, peripheral blood, cord blood, and liver are susceptible to infection by HIV-1 and may serve as reservoirs for transmitting the virus throughout the body. In contrast to lymphocytes, the chronic and low-level mode of infection that HIV-1 takes on within monocytes/macrophages allows these cells to contribute to persistent viral infection. Infection of these cells by HIV-1 can alter a variety of their immunological functions such as cytokine production, chemotaxis, accessory cell function, and microbicidal activity. Furthermore, macrophages and macrophage-related microglial cells in the brain and CSF are thought to play a critical role in the pathogenesis of CNS disease. Infection with HIV-1 in monocytes/macrophages is regulated in an autocrine manner by a panel of cytokines and other soluble factors. Most HIV-1 isolates exhibit specific tropism for monocytes/macrophages, lymphocytes, or, in some cases, both cell types; this phenomenon of tropism may be linked to structural variabilities between different isolates. While in vitro studies clearly demonstrate that the replicating cycle of HIV-1 in monocytes/macrophages differs from its replicating cycle in lymphocytes, elucidation of the role of monocyte/macrophages in mediating the severe immunosuppression characteristic of AIDS is far more from complete, and further investigation into the role of monocytes/macrophages in the immunopathogenesis of HIV-1 infection is necessary to design therapeutic approaches to control viral infection and disease progression.