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Cancer stem cells (CSCs) are of fundamental importance in tumor progression because of their tumor-initiating properties, their resistance to radio- and chemotherapy, their invasive properties and their propensity to escape immune responses that together contribute to tumor relapse. These highly aggressive features underscore the importance of constantly identifying new and innovative therapeutic solutions to eradicate these cells. In this narrative review we discuss recent findings on the involvement of PARP family members in cancer stem cell biology and the benefit of their inhibition. Nonetheless, an important limitation in the use of PARP inhibitors is the emergence of a prominent function of PARP1 in non-cancer stem cell biology including stem cell maintenance and differentiation during development, neurogenesis or adipogenesis. Thus, we also summarize the dominant discoveries revealing the importance of PARP1 in normal stem cell biology.