Redox metabolism plays a central role in the cellular metabolism network, involves catabolic and anabolic reactions of diverse biomass, and determines the redox state of cells. It can be quantitatively and conveniently measured in living cells and organisms with genetically encoded fluorescent sensors, providing novel insights that cannot be readily acquired via conventional metabolic assays. Here, we review the recent progress on the regulation of leukemogenesis via redox metabolism, especially redox biosensor-based findings. In general, low reactive oxygen species levels and high reductive capacity promote leukemogenesis and chemotherapy resistance in leukemia cells, and acute leukemia cells rewire metabolism of glucose, fatty acids, and some amino acids, together with oxidative phosphorylation, to fuel energy production, support biomass-related synthesis, and survive oxidative stress. In summary, redox metabolism is a potential target for the development of novel therapies for leukemia or beneficial dietary regimens for patients with refractory and relapsed leukemia.