Reactive oxygen species (ROS) have traditionally been viewed as harmful byproducts of cellular metabolism, contributing to various human pathologies. However, recent research indicates that ROS play critical roles in cellular signaling pathways. Mitochondria are a major source of ROS, which are produced through the electron transport chain and other mitochondrial enzymes. These ROS integrate cellular energy status, metabolite concentrations, and upstream signaling events, influencing cellular stress responses, stem cell maintenance, survival, and oncogenic transformation. In hypoxia, mitochondrial ROS production is essential for the cellular response, stabilizing hypoxia-inducible factors (HIFs) and regulating Na+/K+-ATPase activity and calcium stores. The PI3-kinase pathway also induces mitochondrial ROS emission, which inhibits mTOR activity and promotes cellular energy conservation. FOXOs, transcription factors regulated by oxidative stress, control antioxidant gene expression and mitochondrial ROS levels, influencing cell cycle arrest, stress resistance, and tumor suppression. Mitochondrial ROS regulate phosphatases by oxidizing cysteine residues, affecting enzyme activity. They also mediate TNFα-induced cell death by inhibiting JNK phosphatases and activating JNK signaling. In cancer, mitochondrial ROS contribute to cellular transformation by promoting oncogenic signaling and metabolic changes. The authors propose a new model where low levels of mitochondrial ROS are necessary for cellular processes, while higher levels trigger senescence or apoptosis. Irreversible damage occurs under extreme ROS conditions. This model challenges the traditional view of ROS as solely detrimental and suggests that ROS may have beneficial roles in certain biological contexts.Reactive oxygen species (ROS) have traditionally been viewed as harmful byproducts of cellular metabolism, contributing to various human pathologies. However, recent research indicates that ROS play critical roles in cellular signaling pathways. Mitochondria are a major source of ROS, which are produced through the electron transport chain and other mitochondrial enzymes. These ROS integrate cellular energy status, metabolite concentrations, and upstream signaling events, influencing cellular stress responses, stem cell maintenance, survival, and oncogenic transformation. In hypoxia, mitochondrial ROS production is essential for the cellular response, stabilizing hypoxia-inducible factors (HIFs) and regulating Na+/K+-ATPase activity and calcium stores. The PI3-kinase pathway also induces mitochondrial ROS emission, which inhibits mTOR activity and promotes cellular energy conservation. FOXOs, transcription factors regulated by oxidative stress, control antioxidant gene expression and mitochondrial ROS levels, influencing cell cycle arrest, stress resistance, and tumor suppression. Mitochondrial ROS regulate phosphatases by oxidizing cysteine residues, affecting enzyme activity. They also mediate TNFα-induced cell death by inhibiting JNK phosphatases and activating JNK signaling. In cancer, mitochondrial ROS contribute to cellular transformation by promoting oncogenic signaling and metabolic changes. The authors propose a new model where low levels of mitochondrial ROS are necessary for cellular processes, while higher levels trigger senescence or apoptosis. Irreversible damage occurs under extreme ROS conditions. This model challenges the traditional view of ROS as solely detrimental and suggests that ROS may have beneficial roles in certain biological contexts.