Ferroptosis is an iron-dependent form of regulated cell death characterized by uncontrolled lipid peroxidation. Since its identification in 2012, ferroptosis has emerged as a crucial mechanism in various physiological and pathological contexts, leading to significant therapeutic advancements. This review summarizes the molecular mechanisms and regulatory pathways of ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. It examines the involvement of ferroptosis in various diseases, 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 various therapies, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Additionally, it discusses pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. The review also elucidates the interplay between ferroptosis and other forms of regulated cell death. Insights from this review hold promise for advancing our understanding of ferroptosis in the context of human health and disease. Keywords: Biomarker, Cancer therapy, Ferroptosis, Human disease, Immunity. Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation and subsequent plasma membrane rupture. It can occur via two primary pathways: the extrinsic pathway, which relies on transporters such as activating TFRC or inhibiting system xc-, and the intrinsic pathway, which is enzyme-regulated, for example, by inhibiting GPX4 or AIFM2. Ferroptosis arises from an imbalance between oxidants and antioxidants, driven by abnormal expression and activity of various redox-active enzymes that either produce or neutralize free radicals and lipid oxidation products. The plasma membrane damage can be repaired by the NINJ1 protein or ESCRT-III machinery. Ferroptosis is driven by iron accumulation and excessive lipid peroxidation, with the chelation of surplus iron and the activation of both GPX4-dependent and -independent antioxidant pathways acting as inhibitory mechanisms against ferroptosis. Lipid peroxidation is a biochemical process where free radicals, such as reactive oxygen species (ROS), attack and oxidize lipids in cell membranes and/or membrane organelles. This process can lead to the formation of lipid peroxides and other reactive compounds, which can further propagate oxidative damage to nearby molecules. Increased production or stimulation of ROS can induce lipid peroxidation, resulting in various forms of RCD. ROS are chemically reactive molecules containing oxygen, generated from various sources, including but not limited to mitochondrial respiratory chain, the Fenton reaction, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), and the enzymatic reaction. These ROS can initiate and/or enhance ferroptosis susceptibility across different cell types or tissues. Mitochondria generate ROS asFerroptosis is an iron-dependent form of regulated cell death characterized by uncontrolled lipid peroxidation. Since its identification in 2012, ferroptosis has emerged as a crucial mechanism in various physiological and pathological contexts, leading to significant therapeutic advancements. This review summarizes the molecular mechanisms and regulatory pathways of ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. It examines the involvement of ferroptosis in various diseases, 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 various therapies, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Additionally, it discusses pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. The review also elucidates the interplay between ferroptosis and other forms of regulated cell death. Insights from this review hold promise for advancing our understanding of ferroptosis in the context of human health and disease. Keywords: Biomarker, Cancer therapy, Ferroptosis, Human disease, Immunity. Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation and subsequent plasma membrane rupture. It can occur via two primary pathways: the extrinsic pathway, which relies on transporters such as activating TFRC or inhibiting system xc-, and the intrinsic pathway, which is enzyme-regulated, for example, by inhibiting GPX4 or AIFM2. Ferroptosis arises from an imbalance between oxidants and antioxidants, driven by abnormal expression and activity of various redox-active enzymes that either produce or neutralize free radicals and lipid oxidation products. The plasma membrane damage can be repaired by the NINJ1 protein or ESCRT-III machinery. Ferroptosis is driven by iron accumulation and excessive lipid peroxidation, with the chelation of surplus iron and the activation of both GPX4-dependent and -independent antioxidant pathways acting as inhibitory mechanisms against ferroptosis. Lipid peroxidation is a biochemical process where free radicals, such as reactive oxygen species (ROS), attack and oxidize lipids in cell membranes and/or membrane organelles. This process can lead to the formation of lipid peroxides and other reactive compounds, which can further propagate oxidative damage to nearby molecules. Increased production or stimulation of ROS can induce lipid peroxidation, resulting in various forms of RCD. ROS are chemically reactive molecules containing oxygen, generated from various sources, including but not limited to mitochondrial respiratory chain, the Fenton reaction, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), and the enzymatic reaction. These ROS can initiate and/or enhance ferroptosis susceptibility across different cell types or tissues. Mitochondria generate ROS as