Sirtuin 1 acts in various cell processes, deacetylating both chromatin and non-histone proteins, and its role in cancer and aging has long been studied and debated. Here we discuss another aspect of SirT1 biology, its function as a stem cell pluripotency and differentiation regulator. We evaluate the implications of these findings in sirtuin inhibition-based cancer treatment and in the application of sirtuin activation for anti-aging therapy.