SummaryIt is thought that monocyte-macrophages and probably dendritic cells play a central role in HIV-1 primary infection, as well as in its evolution, given that they are among the first cells infected and later function as important reservoirs for the virus. These cells may participate in the selection of certain viral strains instead of others. Levels of CCR5 coreceptor expression on the surface of monocytes and macrophages determine their susceptibility to infection by HIV-1 strains using this coreceptor and may explain, in part, the differences in the infectivity of these cells through the maturation process. However, selection for certain strains is not only determined by the level of coreceptor expression, but by the biochemical properties of the different coreceptors and their relationship with other surface molecules and the chemokine and cytokine networks, which also influence the selective viral infection and replication in these cells. Any current or newly designed therapies need to be evaluated, including careful analysis of the levels of HIV-1 infection of the cells of the monocyte-macrophage lineage, because these cells are both significant viral reservoirs and a center of virus production at all stages of the disease.