ATP-binding transporters (ABC-t) play various roles in regulation of organism function and homeostasis from prokaryote to mammals. ABC-t mediate transport mainly of lipophilic substances through cellular membranes. These transporters protect stem cells against toxic substances of either endogenous, or importantly, exogenous origin. These transporters are called ABC-t associated with multi-drug resistance (MDR), according to their role in multidrug resistance to pharmacotherapy. High level of ABC-t expression is a typical feature of stem cells and many types of cancer stem cells. Particularly, ABCB1/P-glycoprotein/MDR1, ABCC1/multidrug resistance-associated protein 1 (MRP1), and ABCG2/BCRP (Breast cancer resistance protein);. However, substrates of ABC-t/MDR are not only toxins, but also important signaling molecules as well as leukotrienes and/or glutathione conjugates; and porphyrins, which mediate balance in intracellular oxidation-reduction processing. Thus we hypothesize the role of ABC-t/MDR in regulation of stem cells fate. To test this hypothesis we analyzed effect of modulation of ABC-t/MDR activity in embryonic and neural stem cells. We observed that ABCC1 and ABCG2 are the most expressed ABC-t/MDR in our tested stem cells. Importantly, inhibition of these ABC-t/MDR leads to decreasing of stemness and induction of differentiation in both embryonic and neural stem cells. Analysis of mechanism of observed effect and identification of studying ABC-t/MDR substrates, which may be responsible for this effect, are in progress.