Vitamin E is a group of essential lipid-soluble vitamin compounds, of which alpha-tocopherol is the most biologically active. It acts as a potent antioxidant in vivo to prevent harmful effects of free radicals generated by lipid peroxidation. Vitamin E is also being increasingly recognized to have multiple nonantioxidant actions in various critical cell functions. Its absorption in small intestine depends on pancreatic enzymes and bile, and uptake into hepatocytes is reliant on alpha-tocopherol transport protein (α-TTP). Vitamin E deficiency is found in conditions with fat malabsorption, such as pancreatic insufficiency, cholestasis, and short gut syndrome. Rare conditions with vitamin E deficiency include Ataxia with vitamin E deficiency (mutations in α-TTP), abetalipoproteinemia and hypobetalipoproteinemia, and chylomicron retention disease. Clinical manifestations can include neuropathies (spinocerebellar dysfunction with ataxia, low or absent reflexes, loss of touch/proprioception), skeletal myopathy, retinal degeneration, and hemolytic anemia. Replacement of vitamin E as part of isolated or fat-soluble vitamin deficiency is critical to prevent these complications. Vitamin E toxicity is rare but very high doses can lead to hemorrhagic effects, potentially through inhibition of platelet aggregation and adhesion.