The susceptibility of developing acute renal failure depends on the ability of the kidney to recover from acute injury and regain normal function. Recently, the possible contribution of stem cells (SCs) to the regeneration of acute tubular injury has been investigated. There is evidence indicating that, under pathophysiological conditions, SCs derived from bone marrow are able to migrate in the injured kidney but they seem to play a minor role in tubular regeneration in regard to the resident cells. However, the administration of ex vivo expanded bone marrow-derived mesenchymal SCs has proven to be beneficial in various experimental models of acute renal failure. The mechanism underlining this beneficial effect is still matter of debate. The transdifferentiation or fusion of SCs to repopulate tubules is considered to play a minor role. The administered SCs may, however, modify the microenvironment by inducing dedifferentiation and proliferation of tubular cells surviving to injury or by allowing expansion of resident SCs. The recent identification of resident progenitor/SC populations in the adult kidney supports the hypothesis that resident SCs may play a critical role in the repair of renal injury. Therefore, therapeutic strategies to exploit the regenerative potential of SCs may be based on the administration of ex vivo expanded SCs or on stimulation of expansion and differentiation of local progenitor/SC populations.