Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor expressed in many cell types, including osteoblasts, osteocytes, and osteoclasts. Nrf2 has been considered a master regulator of cytoprotective genes against oxidative and chemical insults. The lack of Nrf2 can induce pathologies in multiple organs. Nrf2 deficiency promotes osteoclast differentiation and osteoclast activity, which leads to an increase in bone resorption. The role of Nrf2 in osteoblast differentiation and osteoblast activity is more complex. Nrf2 mediates anabolic effects within an ideal range. Nrf2 deletion suppresses load induced bone formation and delays fracture healing. Overall, Nrf2 plays an important role in the regulation of bone homeostasis in bone cells.