Nuclear factor erythroid 2-related factor 2 (Nrf2) is ubiquitously expressed in most eukaryotic cells and functions to induce a broad range of cellular defenses against exogenous and endogenous stresses, including oxidants, xenobiotics, and excessive nutrient/metabolite supply. Because the production and fate of stem cells are often modulated by cellular redox and metabolic homeostasis, important roles of Nrf2 have emerged in the regulation of stem cell quiescence, survival, self-renewal, proliferation, senescence, and differentiation. In a rapidly advancing field, this review summarizes Nrf2 signaling in the context of stem cell state and function and provides a rationale for Nrf2 as a therapeutic target in stem cell-based regenerative medicine. As a cellular metabolic and stress sensor, the transcription factor Nrf2 is a pivotal regulator of stem cell self-renewal, proliferation, and differentiation.Nrf2 displays cell type-specific and/or stage-dependent impact on stem cell biology in response to various environmental cues.Nrf2 modulates PSCs through the regulation of pluripotency factors, metabolism, redox homeostasis, and cellular stress responses.Nrf2 maintain ASCs self-renewal, quiescence, and regenerative capacity while protecting against ASC depletion in response to stress and aging.