Reactive oxygen species (ROS) are produced during normal metabolism and xenobiotic exposure, and their concentrations can be beneficial or harmful to cells and tissues. At physiological low levels, ROS function as redox messengers in intracellular signaling and regulation. However, excess ROS can induce oxidative modification of cellular macromolecules, inhibit protein function, and promote cell death. Various redox systems, such as the glutathione, thioredoxin, and pyridine nucleotide redox couples, participate in cell signaling and modulation of cell function, including apoptotic cell death. Apoptosis is initiated by extracellular and intracellular signals via two main pathways: the death receptor- or mitochondria-mediated pathways. Pathologies can result from oxidative stress-induced apoptotic signaling due to increased ROS, decreased antioxidants, disruption of intracellular redox homeostasis, and irreversible oxidative modifications of lipid, protein, or DNA. This review focuses on key aspects of ROS and redox mechanisms in apoptotic signaling, highlighting gaps in knowledge and potential avenues for further investigation. Understanding redox control of apoptotic initiation and execution could underpin the development of therapeutic interventions for oxidative stress-associated disorders.Reactive oxygen species (ROS) are produced during normal metabolism and xenobiotic exposure, and their concentrations can be beneficial or harmful to cells and tissues. At physiological low levels, ROS function as redox messengers in intracellular signaling and regulation. However, excess ROS can induce oxidative modification of cellular macromolecules, inhibit protein function, and promote cell death. Various redox systems, such as the glutathione, thioredoxin, and pyridine nucleotide redox couples, participate in cell signaling and modulation of cell function, including apoptotic cell death. Apoptosis is initiated by extracellular and intracellular signals via two main pathways: the death receptor- or mitochondria-mediated pathways. Pathologies can result from oxidative stress-induced apoptotic signaling due to increased ROS, decreased antioxidants, disruption of intracellular redox homeostasis, and irreversible oxidative modifications of lipid, protein, or DNA. This review focuses on key aspects of ROS and redox mechanisms in apoptotic signaling, highlighting gaps in knowledge and potential avenues for further investigation. Understanding redox control of apoptotic initiation and execution could underpin the development of therapeutic interventions for oxidative stress-associated disorders.