Ferroptosis is a regulated form of cell death driven by the loss of activity of glutathione peroxidase 4 (GPX4) and the subsequent accumulation of lipid-based reactive oxygen species, particularly lipid hydroperoxides. This iron-dependent cell death is distinct from other modalities such as apoptosis, necrosis, and necroptosis. The discovery of ferroptosis was made through high-throughput screening, where erastin and RSL3 were identified as compounds that induce this form of cell death. These compounds were found to be non-apoptotic and required cellular iron and lipophilic antioxidants to suppress their effects. Key regulators of ferroptosis include system x_c^- inhibitors, glutathione depleters, and direct GPX4 inhibitors. Additional pathways modulating ferroptosis include the mevalonate pathway and the transsulfuration pathway. Ferroptosis has been implicated in various pathological conditions, including acute kidney injury, Huntington's disease, periventricular leukomalacia, and cancer. The role of ferroptosis in development and its potential therapeutic applications are also discussed.Ferroptosis is a regulated form of cell death driven by the loss of activity of glutathione peroxidase 4 (GPX4) and the subsequent accumulation of lipid-based reactive oxygen species, particularly lipid hydroperoxides. This iron-dependent cell death is distinct from other modalities such as apoptosis, necrosis, and necroptosis. The discovery of ferroptosis was made through high-throughput screening, where erastin and RSL3 were identified as compounds that induce this form of cell death. These compounds were found to be non-apoptotic and required cellular iron and lipophilic antioxidants to suppress their effects. Key regulators of ferroptosis include system x_c^- inhibitors, glutathione depleters, and direct GPX4 inhibitors. Additional pathways modulating ferroptosis include the mevalonate pathway and the transsulfuration pathway. Ferroptosis has been implicated in various pathological conditions, including acute kidney injury, Huntington's disease, periventricular leukomalacia, and cancer. The role of ferroptosis in development and its potential therapeutic applications are also discussed.