Lipid peroxidation is a process where oxidants attack lipids with carbon-carbon double bonds, especially polyunsaturated fatty acids (PUFAs). This process has been extensively studied over the past four decades, revealing its significant role in cell biology and human health. The review focuses on the biochemical aspects of lipid peroxidation, particularly the production, metabolism, and signaling mechanisms of two main products: malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE). These products have both physiological and cytotoxic roles, acting as signaling molecules that regulate gene expression and cell survival, while also inhibiting gene expression and promoting cell death. The review also discusses in vivo mammalian models and common pathological processes linked to MDA and 4-HNE. Lipids are divided into apolar and polar groups. Apolar lipids, such as triglycerides, are stored in adipose tissue, while polar lipids form the structural components of cell membranes. Lipids also function as signaling molecules, with enzymes like lipoxygenase, cyclooxygenase, and cytochrome P-450 generating various signaling mediators. These signaling molecules include diacylglycerol (DAG), inositol phosphates, sphingosine-1-phosphate, prostaglandins, phosphatidylserine, and steroid hormones. Reactive oxygen species (ROS), such as hydroxyl radicals and hydroperoxyl radicals, can cause lipid peroxidation, leading to oxidative damage. The process of lipid peroxidation involves three steps: initiation, propagation, and termination. During initiation, prooxidants abstract hydrogen from lipids, forming lipid radicals. In propagation, these radicals react with oxygen to form lipid peroxy radicals, which abstract hydrogen from other lipids, continuing the chain reaction. Termination involves antioxidants like vitamin E donating a hydrogen atom to the peroxy radical, forming nonradical products. Lipid peroxidation produces various oxidation products, with MDA and 4-HNE being the most studied. MDA is a major product of lipid peroxidation and is used as a biomarker for oxidative stress. It can form adducts with proteins and DNA, leading to biomolecular damage. 4-HNE is a highly reactive aldehyde that acts as both a signaling molecule and a cytotoxic product. It can modify proteins and DNA, leading to various pathological conditions. MDA is metabolized through enzymatic and nonenzymatic processes, leading to the formation of various metabolites. 4-HNE is also metabolized through enzymatic and nonenzymatic pathways, with its metabolism leading to the formation of corresponding alcohols, acids, and conjugate products. Both MDA and 4-HNE have significant roles in cellular signaling and pathology, with their levels linked to various diseases. The review highlights the importance of understanding theLipid peroxidation is a process where oxidants attack lipids with carbon-carbon double bonds, especially polyunsaturated fatty acids (PUFAs). This process has been extensively studied over the past four decades, revealing its significant role in cell biology and human health. The review focuses on the biochemical aspects of lipid peroxidation, particularly the production, metabolism, and signaling mechanisms of two main products: malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE). These products have both physiological and cytotoxic roles, acting as signaling molecules that regulate gene expression and cell survival, while also inhibiting gene expression and promoting cell death. The review also discusses in vivo mammalian models and common pathological processes linked to MDA and 4-HNE. Lipids are divided into apolar and polar groups. Apolar lipids, such as triglycerides, are stored in adipose tissue, while polar lipids form the structural components of cell membranes. Lipids also function as signaling molecules, with enzymes like lipoxygenase, cyclooxygenase, and cytochrome P-450 generating various signaling mediators. These signaling molecules include diacylglycerol (DAG), inositol phosphates, sphingosine-1-phosphate, prostaglandins, phosphatidylserine, and steroid hormones. Reactive oxygen species (ROS), such as hydroxyl radicals and hydroperoxyl radicals, can cause lipid peroxidation, leading to oxidative damage. The process of lipid peroxidation involves three steps: initiation, propagation, and termination. During initiation, prooxidants abstract hydrogen from lipids, forming lipid radicals. In propagation, these radicals react with oxygen to form lipid peroxy radicals, which abstract hydrogen from other lipids, continuing the chain reaction. Termination involves antioxidants like vitamin E donating a hydrogen atom to the peroxy radical, forming nonradical products. Lipid peroxidation produces various oxidation products, with MDA and 4-HNE being the most studied. MDA is a major product of lipid peroxidation and is used as a biomarker for oxidative stress. It can form adducts with proteins and DNA, leading to biomolecular damage. 4-HNE is a highly reactive aldehyde that acts as both a signaling molecule and a cytotoxic product. It can modify proteins and DNA, leading to various pathological conditions. MDA is metabolized through enzymatic and nonenzymatic processes, leading to the formation of various metabolites. 4-HNE is also metabolized through enzymatic and nonenzymatic pathways, with its metabolism leading to the formation of corresponding alcohols, acids, and conjugate products. Both MDA and 4-HNE have significant roles in cellular signaling and pathology, with their levels linked to various diseases. The review highlights the importance of understanding the