Ferroptosis, a novel form of regulated cell death driven by iron overload, loss of antioxidant defenses, and lipid peroxidation, has gained attention for its role in doxorubicin-induced cardiotoxicity. Preclinical evidence supports the pathophysiologic role of ferroptosis in this condition, and modulation of ferroptosis with specific inhibitors offers new therapeutic opportunities. This review discusses the molecular mechanisms and therapeutic potential of targeting ferroptosis in doxorubicin-induced cardiotoxicity. Key metabolic pathways involved in ferroptosis, including iron, glutathione (GSH), and lipid metabolism, are reviewed. Iron overload, driven by increased iron intake and decreased export, is a critical factor in doxorubicin-induced cardiotoxicity. GSH depletion and inactivation of glutathione peroxidase 4 (GPX4) are also crucial, as they lead to lipid peroxidation and ferroptosis. Lipid metabolism, particularly the accumulation of polyunsaturated fatty acid (PUFA)-containing phospholipids, plays a significant role in ferroptosis. Recent studies have shown that ferroptosis inhibitors, such as iron chelators (e.g., dexrazoxane), radical-trapping antioxidants (e.g., ferrostatin-1), GSH precursors (e.g., N-acetylcysteine), and Nrf2 activators (e.g., fisetin), are effective in preventing and treating doxorubicin-induced cardiotoxicity. However, challenges remain, including the potential risk of tumor growth and metastasis associated with ferroptosis inhibition, the need for reliable serum biomarkers, and the exploration of ferroptosis in various cardiac cell types. Further research is essential to fully understand the role of ferroptosis and develop targeted therapies for doxorubicin-induced cardiotoxicity.Ferroptosis, a novel form of regulated cell death driven by iron overload, loss of antioxidant defenses, and lipid peroxidation, has gained attention for its role in doxorubicin-induced cardiotoxicity. Preclinical evidence supports the pathophysiologic role of ferroptosis in this condition, and modulation of ferroptosis with specific inhibitors offers new therapeutic opportunities. This review discusses the molecular mechanisms and therapeutic potential of targeting ferroptosis in doxorubicin-induced cardiotoxicity. Key metabolic pathways involved in ferroptosis, including iron, glutathione (GSH), and lipid metabolism, are reviewed. Iron overload, driven by increased iron intake and decreased export, is a critical factor in doxorubicin-induced cardiotoxicity. GSH depletion and inactivation of glutathione peroxidase 4 (GPX4) are also crucial, as they lead to lipid peroxidation and ferroptosis. Lipid metabolism, particularly the accumulation of polyunsaturated fatty acid (PUFA)-containing phospholipids, plays a significant role in ferroptosis. Recent studies have shown that ferroptosis inhibitors, such as iron chelators (e.g., dexrazoxane), radical-trapping antioxidants (e.g., ferrostatin-1), GSH precursors (e.g., N-acetylcysteine), and Nrf2 activators (e.g., fisetin), are effective in preventing and treating doxorubicin-induced cardiotoxicity. However, challenges remain, including the potential risk of tumor growth and metastasis associated with ferroptosis inhibition, the need for reliable serum biomarkers, and the exploration of ferroptosis in various cardiac cell types. Further research is essential to fully understand the role of ferroptosis and develop targeted therapies for doxorubicin-induced cardiotoxicity.