HIV-1 exerts its most profound effects through destruction of the host's immune responses specifically through targeting of the T-lymphocyte populations. In addition to its primary immune target, HIV-1 also targets cells of the nervous, skeletal and vascular system. There is emerging evidence to suggest that HIV-1 may, in part at least, affect these diverse tissues by impairing the homeostatic production of terminally differentiated cells from stem and progenitor cell populations. The interaction between HIV-1 and stem cell populations may serve to underpin the diverse nonimmunological effects of HIV-1. This review deals with the effect of HIV-1 infection on a number of progenitor cell types, with emphasis on delineating mechanisms of HIV's destructive effect on the body. Modification of these effects may represent novel avenues for exploration in our search for clinical interventions.