HIV-1 can establish both long lived and productive infection of macrophages (Mφ) but circulating monocytes are less permissive to infection. Multiple studies have identified extensive changes to monocyte and Mφ phenotype, differentiation or function. These include alterations in Toll-like receptor signaling and resultant changes to cytokine responses, specific defects in phagocytosis and microbial killing and modulation of apoptotic responses, all of which may perturb the important role of these cells in innate immunity. Interpretation of contradictory data however, is complicated by the use of different experimental models and many of the reported effects may be an indirect consequence of HIV-1 infection that result from exposure to viral products or from disruption of cellular and cytokine networks in the immune system, rather than the direct consequence of productive HIV-1 infection. Future research should focus on refining experimental models and on elucidating the physiological mechanisms of monocyte/ Mφ dysfunction during HIV-1 infection. © 2010 Bentham Science Publishers Ltd.