Certain bacterial toxins and type-III-translocated virulence factors have a peculiar property: they exert part of their actions by modulating Rho GTPases. These toxins target the actin cytoskeleton of host cells and reorganize it to their own advantage, either to facilitate macropinocytosis, which is required for invasive bacteria to enter cells, or to block pathogen sequestration by macrophages. In addition, by acting on Rho GTPases, bacteria may also interfere with the fate of host cells, favoring survival or death depending on their needs. Rho GTPases control the activation of NF-kappaB, which is involved in the expression of antiapoptotic proteins and mediates immunological responses as well. Here, we give a perspective on how NF-kappaB may participate in linking Rho-acting toxins and apoptosis.