Ferroptosis, an iron-dependent form of regulated cell death, plays a critical role in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. This review summarizes the molecular mechanisms and therapeutic potential of targeting ferroptosis in DOX-induced cardiotoxicity. DOX, a member of the anthracycline family, is a widely used chemotherapeutic agent but causes dose-dependent cardiotoxicity, including acute and chronic forms. Acute cardiotoxicity is characterized by left ventricular dysfunction, arrhythmias, and electrocardiographic abnormalities, while chronic cardiotoxicity leads to cardiac enlargement, ventricular dilation, and heart failure. Current treatments for DOX-induced cardiotoxicity include dexrazoxane, which works through iron chelation, antioxidant effects, and DNA damage inhibition, but these therapies are not highly specific to the molecular pathways involved in DOX-induced cardiotoxicity. Ferroptosis is driven by iron overload, loss of antioxidant defenses, and lipid peroxidation. It involves the interplay of iron, glutathione, and lipid metabolism. Ferroptosis is characterized by cell swelling, condensed mitochondria, and increased mitochondrial membrane densities. Key factors in ferroptosis include iron homeostasis, glutathione (GSH) metabolism, and lipid metabolism. The enzyme glutathione peroxidase 4 (GPX4) is essential for preventing lipid peroxidation, and its inhibition leads to ferroptosis. Ferroptosis is also influenced by the iron regulatory protein (IRP)-iron response element (IRE) system, which regulates iron homeostasis. DOX induces iron overload by up-regulating iron import and down-regulating iron export. This leads to increased labile iron pool (LIP) and lipid peroxidation, contributing to ferroptosis. DOX also impairs heme synthesis and degradation, leading to iron overload and ferroptosis. The molecular mechanisms of DOX-induced cardiotoxicity involve the dysregulation of iron metabolism, GSH metabolism, and lipid metabolism. Ferroptosis is a key contributor to DOX-induced cardiotoxicity, and targeting ferroptosis with specific inhibitors may provide new therapeutic opportunities. Several drugs, including iron chelators like dexrazoxane and ferroptosis inhibitors like Fer-1, have shown potential in preventing and treating DOX-induced cardiotoxicity. Nrf2 activators, GSH precursors, and AMPK activators also play a role in mitigating ferroptosis. However, further research is needed to identify reliable biomarkers for ferroptosis in DOX-induced cardiotoxicity and to explore the roles of ferroptosis in various cardiac cell types. The development of ferroptosis-targeted therapies holds promise for the management of DOX-induced cardiotoxicity and other cardiovascular diseases.Ferroptosis, an iron-dependent form of regulated cell death, plays a critical role in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. This review summarizes the molecular mechanisms and therapeutic potential of targeting ferroptosis in DOX-induced cardiotoxicity. DOX, a member of the anthracycline family, is a widely used chemotherapeutic agent but causes dose-dependent cardiotoxicity, including acute and chronic forms. Acute cardiotoxicity is characterized by left ventricular dysfunction, arrhythmias, and electrocardiographic abnormalities, while chronic cardiotoxicity leads to cardiac enlargement, ventricular dilation, and heart failure. Current treatments for DOX-induced cardiotoxicity include dexrazoxane, which works through iron chelation, antioxidant effects, and DNA damage inhibition, but these therapies are not highly specific to the molecular pathways involved in DOX-induced cardiotoxicity. Ferroptosis is driven by iron overload, loss of antioxidant defenses, and lipid peroxidation. It involves the interplay of iron, glutathione, and lipid metabolism. Ferroptosis is characterized by cell swelling, condensed mitochondria, and increased mitochondrial membrane densities. Key factors in ferroptosis include iron homeostasis, glutathione (GSH) metabolism, and lipid metabolism. The enzyme glutathione peroxidase 4 (GPX4) is essential for preventing lipid peroxidation, and its inhibition leads to ferroptosis. Ferroptosis is also influenced by the iron regulatory protein (IRP)-iron response element (IRE) system, which regulates iron homeostasis. DOX induces iron overload by up-regulating iron import and down-regulating iron export. This leads to increased labile iron pool (LIP) and lipid peroxidation, contributing to ferroptosis. DOX also impairs heme synthesis and degradation, leading to iron overload and ferroptosis. The molecular mechanisms of DOX-induced cardiotoxicity involve the dysregulation of iron metabolism, GSH metabolism, and lipid metabolism. Ferroptosis is a key contributor to DOX-induced cardiotoxicity, and targeting ferroptosis with specific inhibitors may provide new therapeutic opportunities. Several drugs, including iron chelators like dexrazoxane and ferroptosis inhibitors like Fer-1, have shown potential in preventing and treating DOX-induced cardiotoxicity. Nrf2 activators, GSH precursors, and AMPK activators also play a role in mitigating ferroptosis. However, further research is needed to identify reliable biomarkers for ferroptosis in DOX-induced cardiotoxicity and to explore the roles of ferroptosis in various cardiac cell types. The development of ferroptosis-targeted therapies holds promise for the management of DOX-induced cardiotoxicity and other cardiovascular diseases.