Ferroptosis is a form of regulated cell death caused by overwhelming lipid peroxidation. The Fenton reaction converts cytosolic hydrogen peroxide or membrane-residing lipid hydroperoxide (L-OOH) into highly reactive hydroxyl radicals, which initiate lipid peroxidation. Alternatively, PUFAs incorporated into the membrane undergo oxidation, resulting in the formation of L-OOH. Multiple mechanisms modulate or inhibit ferroptosis. System Xc⁻ imports cystine into the cell, which is reduced to cysteine, the rate-limiting precursor for GSH synthesis. Alternatively, methionine may be used to generate cysteine via the methionine cycle and TSS pathway. GPX4 uses GSH to reduce L-OOH to nontoxic lipid alcohols, thereby protecting cellular membranes from oxidative damage. Other antioxidant defense systems, such as the FSP1-CoQ10 system and BH4/BH2, independently suppress ROS accumulation and inhibit ferroptosis. IKE, imidazole ketone erastin; PUFA-PL, polyunsaturated fatty acid phospholipid; TSS, transulfuration; FSP1, ferroptosis suppressor protein 1; BH4/BH2, tetrahydrobiopterin/dihydrobiopterin; HMG-CoA; 3-hydroxy-3-methylglutaryl-coenzyme A; Ac-CoA; acetyl CoA.