The pathogenesis of HIV infection and the definition of the cell types target of HIV is the crucial background for the improvement of the therapeutic strategies against HIV infection. Monocyte-macrophages (M/M) are easily infected by HIV, and play a crucial role in the maintenance and the progression of HIV-related disease; HIV infection of M/M is the principal cause of HIV-related "dementia complex". Thus it is crucial that drugs used in the therapy of HIV infection are active against HIV replicating in cells of M/M lineage. In this paper the interaction between HIV and M/M is analyzed and the characteristics of viral replication in these cells, and the in vitro antiviral activity of several drugs in M/M are discussed. These data suggest that patients should be treated with drugs, that inhibit HIV also in M/M and, consequently, are able to block the clinical manifestations related to M/M infection, such as "dementia complex".