Ferroptosis is a recently identified form of regulated cell death characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism. It can be induced by experimental compounds and clinical drugs in cancer cells and certain normal cells. The process involves the activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, upregulation of endoplasmic reticulum stress, and inhibition of the cystine/glutamate antiporter. Iron chelators and lipid peroxidation inhibitors can pharmacologically inhibit ferroptosis. Glutathione peroxidase 4, heat shock protein beta-1, and nuclear factor erythroid 2-related factor 2 function as negative regulators, while NADPH oxidase and p53 act as positive regulators. Misregulated ferroptosis has been implicated in various physiological and pathological processes, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, and T-cell immunity. This review summarizes the regulation mechanisms and signaling pathways of ferroptosis and discusses its role in disease.Ferroptosis is a recently identified form of regulated cell death characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism. It can be induced by experimental compounds and clinical drugs in cancer cells and certain normal cells. The process involves the activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, upregulation of endoplasmic reticulum stress, and inhibition of the cystine/glutamate antiporter. Iron chelators and lipid peroxidation inhibitors can pharmacologically inhibit ferroptosis. Glutathione peroxidase 4, heat shock protein beta-1, and nuclear factor erythroid 2-related factor 2 function as negative regulators, while NADPH oxidase and p53 act as positive regulators. Misregulated ferroptosis has been implicated in various physiological and pathological processes, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, and T-cell immunity. This review summarizes the regulation mechanisms and signaling pathways of ferroptosis and discusses its role in disease.