α-Tocopherol, the most biologically active form of vitamin E, plays a central role in maintaining animal well-being and enhancing performance through its potent antioxidant function. This review explores the nutritional significance of α-tocopherol in animal systems, with a focus on its bioavailability, biopotency, and broader physiological roles. Among the eight vitamin E vitamers, α-tocopherol is preferentially retained and distributed due to its selective binding by hepatic α-tocopherol transfer protein, which facilitates its incorporation into very-low-density lipoproteins and delivery to tissues. Its antioxidant activity is closely linked to its membrane localization, where it scavenges lipid peroxyl radicals and prevents oxidative damage. The tocopheroxyl radical formed in this process can be regenerated in an antioxidant network by co-antioxidants such as vitamin C, preserving its antioxidant capacity. These molecular mechanisms support membrane integrity, immune function, and metabolic stability, especially under oxidative stress conditions common in livestock production. Despite its well-established importance, the bioavailability and biopotency of α-tocopherol are influenced by several factors, such as chemical form, dietary composition, species-specific gastrointestinal physiology, digestive efficiency, tissue distribution, metabolism, and excretion. α-Tocopherol has the highest biopotency of all vitamin E forms. Thereby, natural RRR-α-tocopherol exhibits greater biopotency than synthetic all-rac-α-tocopherol due to stereoisomer-specific differences in tissue distribution and retention. Esterified forms such as α-tocopheryl acetate, though more stable in feed, require enzymatic hydrolysis for absorption affecting bioavailability, which may be impaired in young or stressed animals. Current challenges include the lack of standardized biomarkers for vitamin E status, limited cross-species biopotency data, and insufficient understanding of how environmental and dietary factors modulate utilization and requirements. This review highlights the need for integrative approaches combining pharmacokinetics, tissue deposition, and functional outcomes to improve the precision of α-tocopherol supplementation strategies. Advancing this understanding is essential to fully harness the nutritional power of α-tocopherol in diverse animal production systems.