Tumor evolution is fueled by mitochondrial oxidative stress. The experiments by Goh et al. directly show that blocking mitochondrial ROS inhibits metastasis, indicating that mitochondrial oxidative stress promotes tumor progression and metastasis. The observed effects most likely involve the effects of ROS on both cancer cells and their surrounding tumor stroma. Cellular processes activated by ROS include DNA damage, autophagy/mitophagy, and aerobic glycolysis. Complementary studies have shown that ROS-induced activation of autophagy and aerobic glycolysis in cancer associated fibroblasts provide recycled nutrients (pyruvate, lactate, ketones, and glutamine, among others) for anabolic cancer cell growth, and protects these cancer cells against apoptosis. Importantly, anti-oxidants will prevent the oxidative stress, reducing tumor progression and metastasis. NAC, N-acetyl-cysteine; SOD2, mitochondrial superoxide dismutase; M-catalase, mitochondrially targeted catalase.