Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, has emerged as a crucial mechanism in various physiological and pathological contexts. This review summarizes the fundamental molecular mechanisms and regulatory pathways underlying ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. Ferroptosis is involved in various pathological conditions, such as cancer, neurodegenerative diseases, sepsis, ischemia-reperfusion injury, autoimmune disorders, and metabolic disorders. The review also explores the role of ferroptosis in response to chemotherapy, radiotherapy, immunotherapy, nanotherapy, and targeted therapy. Additionally, it discusses pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. Finally, the interplay between ferroptosis and other forms of regulated cell death is elucidated, highlighting the promise of advancing our understanding of ferroptosis in the context of human health and disease.Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, has emerged as a crucial mechanism in various physiological and pathological contexts. This review summarizes the fundamental molecular mechanisms and regulatory pathways underlying ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. Ferroptosis is involved in various pathological conditions, such as cancer, neurodegenerative diseases, sepsis, ischemia-reperfusion injury, autoimmune disorders, and metabolic disorders. The review also explores the role of ferroptosis in response to chemotherapy, radiotherapy, immunotherapy, nanotherapy, and targeted therapy. Additionally, it discusses pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. Finally, the interplay between ferroptosis and other forms of regulated cell death is elucidated, highlighting the promise of advancing our understanding of ferroptosis in the context of human health and disease.