Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in cell signaling and immune responses. However, an imbalance between ROS production and cellular antioxidant defenses can lead to oxidative stress, damaging essential cellular components and potentially causing oxidative cell death. This form of cell death includes various subtypes such as ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, and oxieptosis, each with distinct genetic, biochemical, and signaling characteristics. The review discusses the origins of ROS, the impact of antioxidant systems on ROS dynamics, and the mechanisms of different types of oxidative cell death. It highlights the potential of targeting key antioxidant proteins, such as SLC7A11, GCLC, GPX4, TXN, and TXNRD, to induce oxidative cell death in cancer cells. The review also explores the challenges and opportunities in developing pharmacological agents to prevent tumorigenesis or treat established cancer through the induction of oxidative cell death.Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in cell signaling and immune responses. However, an imbalance between ROS production and cellular antioxidant defenses can lead to oxidative stress, damaging essential cellular components and potentially causing oxidative cell death. This form of cell death includes various subtypes such as ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, and oxieptosis, each with distinct genetic, biochemical, and signaling characteristics. The review discusses the origins of ROS, the impact of antioxidant systems on ROS dynamics, and the mechanisms of different types of oxidative cell death. It highlights the potential of targeting key antioxidant proteins, such as SLC7A11, GCLC, GPX4, TXN, and TXNRD, to induce oxidative cell death in cancer cells. The review also explores the challenges and opportunities in developing pharmacological agents to prevent tumorigenesis or treat established cancer through the induction of oxidative cell death.