Vitamin E is a lipid-soluble antioxidant that inhibits lipid peroxidation by scavenging reactive oxygen species, and it is thought to protect against the aging process. Indeed, it is one of the most popular supplements in the US. However, recent studies have revealed that vitamin E has dual effects on the aging process. We discovered that α-tocopherol, the major form of vitamin E in the body, stimulates osteoclast fusion and bone resorption as well as induces an osteoporosis-like phenotype in rodents. Clinical intervention trials have also demonstrated that supplementation with vitamin E is neutral or even harmful for preventing age-related diseases in humans. Therefore, the role of vitamin E as an ‘anti-ager' has been called into question. This review outlines the present understanding of the role of vitamin E in age-related disease prevention.