Ferroptosis is a recently recognized form of regulated cell death characterized by morphological features such as smaller mitochondria, condensed mitochondrial membranes, and outer mitochondrial membrane rupture. It is induced by various compounds, including erastin, RSL3, and BSO, and is associated with lipid peroxidation and reactive oxygen species (ROS) derived from iron metabolism. Ferroptosis is regulated by several molecules, including glutathione peroxidase 4 (GPX4), heat shock protein beta-1 (HSPB1), and nuclear factor erythroid 2-related factor 2 (NRF2), which act as negative regulators by limiting ROS production and iron uptake. In contrast, NADPH oxidase and p53 act as positive regulators by promoting ROS production and inhibiting the cystine/glutamate antiporter SLC7A11. Misregulated ferroptosis is implicated in various physiological and pathological processes, including cancer, neurodegenerative diseases, and drug-induced toxicity. The review summarizes the regulation mechanisms and signaling pathways of ferroptosis and discusses its role in disease. Ferroptosis is distinct from other forms of regulated cell death (RCD) such as apoptosis, necroptosis, and autophagy at morphological, biochemical, and genetic levels. Key regulators include VDAC2/3, GPX4, and SLC7A11, which influence iron metabolism and lipid peroxidation. Ferroptosis is involved in cancer cell death, neurotoxicity, and tissue injury. The review also discusses the role of ferroptosis in disease and the need to identify the signaling pathways and executors of iron-dependent ROS metabolism to distinguish ferroptosis from other types of RCD. The study highlights the importance of ferroptosis in sterile inflammatory conditions and its potential for therapeutic intervention in cancer and injury-associated diseases.Ferroptosis is a recently recognized form of regulated cell death characterized by morphological features such as smaller mitochondria, condensed mitochondrial membranes, and outer mitochondrial membrane rupture. It is induced by various compounds, including erastin, RSL3, and BSO, and is associated with lipid peroxidation and reactive oxygen species (ROS) derived from iron metabolism. Ferroptosis is regulated by several molecules, including glutathione peroxidase 4 (GPX4), heat shock protein beta-1 (HSPB1), and nuclear factor erythroid 2-related factor 2 (NRF2), which act as negative regulators by limiting ROS production and iron uptake. In contrast, NADPH oxidase and p53 act as positive regulators by promoting ROS production and inhibiting the cystine/glutamate antiporter SLC7A11. Misregulated ferroptosis is implicated in various physiological and pathological processes, including cancer, neurodegenerative diseases, and drug-induced toxicity. The review summarizes the regulation mechanisms and signaling pathways of ferroptosis and discusses its role in disease. Ferroptosis is distinct from other forms of regulated cell death (RCD) such as apoptosis, necroptosis, and autophagy at morphological, biochemical, and genetic levels. Key regulators include VDAC2/3, GPX4, and SLC7A11, which influence iron metabolism and lipid peroxidation. Ferroptosis is involved in cancer cell death, neurotoxicity, and tissue injury. The review also discusses the role of ferroptosis in disease and the need to identify the signaling pathways and executors of iron-dependent ROS metabolism to distinguish ferroptosis from other types of RCD. The study highlights the importance of ferroptosis in sterile inflammatory conditions and its potential for therapeutic intervention in cancer and injury-associated diseases.