The liver exhibits the remarkable capacity to regenerate. The process of liver regeneration is multifaceted, as it requires a complex tissue comprised of multiple cell types to sense the extent of injury and mount an appropriate compensatory regrowth response. The inability to regenerate following liver injury can lead to maladaptive scarring of the organ or liver failure, and this represents a significant health and economic burden in Australia. Consequently, there is a need to better understand the molecular and cellular mechanisms that initiate liver regeneration. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that plays a pivotal role in the cell’s adaptation to stress. We previously identified that stimulation of the Nrf2 pathway upon liver injury facilitates regeneration. Recently, we have pioneered the use of integrated metabolomic and transcriptomic profiling in zebrafish to identify how metabolic remodelling impacts organ growth. We now have evidence that Nrf2 plays a key role in the metabolic remodelling that occurs upon liver injury and is required for liver regeneration. The rationale for our work is that an appreciation of the role that Nrf2 and metabolism play in liver regeneration may reveal critical new insights into the metabolic networks that can be targeted for regenerative medicine.