Host factors have a great influence on the susceptibility to HIV or the rate of HIV disease progression. In particular, cytokine/chemokine networks have been shown to variably modulate HIV infection. Of note are the facts that certain chemokine receptors serve as HIV entry coreceptors and that ligands for these receptors inhibit HIV infection through competition for the coreceptors. The effects of pleiotropic cytokine/ chemokine networks on HIV infection, however, appear to be dependent on the virus strains and the cell types being infected. Certain cytokines/chemokines have dichotomous effects on infection with macrophage-tropic and T-cell-tropic HIV-1, or differently modulate HIV infection of macrophages, as compared to that of CD4+ T cells. A further investigation of roles of cytokine/ chemokine networks in HIV infection and delineation of the mechanisms of the cytokine/ chemokine-mediated effects on HIV infection will extend our understanding of the pathogenesis of HIV disease, and may yield novel therapeutic strategies for intervention in HIV disease.