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The existence of cancer stem cells (CSCs) has been already established in several hematopoietic and non-hematopoietic cancers. Chemoresistance has also been demonstrated as a major cause of cancer treatment failure. Although chemotherapy kills most cells in a tumor, it is believed to leave CSCs behind which might be an important mechanism of resistance and thereby cancer treatment failure. The quiescent nature and existence of adenosine triphosphate (ATP)-binding cassette (ABC) drug transporters in CSCs have been suggested to protect them from chemotherapeutic agents. Gaining a better insight into the mechanisms of CSCs chemoresistance might therefore lead to new therapeutic targets and development of better anticancer strategies. Keywords: Cancer stem cells, Chemotherapy, Drug resistance.