Human sebum is produced by sebaceous glands and reaches the skin surface via secretion through the hair shaft. There is experimental evidence that the sebaceous glands and sebum serve as a transport mechanism taking the lipophilic antioxidant vitamin E from the blood to the skin surface. The highest levels of vitamin E are found in the sebum and in the skin lipid film in sebum-rich areas such as facial skin. Recent studies indicate that daily oral supplementation of moderate doses of alpha-tocopherol for at least 3 weeks leads to significant increases of vitamin E levels in human skin sites with a high density of sebaceous glands, such as the face. Thus, the potential photoprotective and antioxidants effects of oral vitamin E, as well as possibly other antioxidants, are site-dependent. These findings should be considered when designing clinical studies to assess the efficacy of oral antioxidants against oxidative stress in the skin.