The main research activities of the last decades on tocopherols were mainly focused on α-tocopherol, in particular when considering the biological activities. However, recent studies have increased the knowledge on γ-tocopherol, which is the major form of vitamin E in the diet in the USA, but not in Europe. γ-Tocopherol provides different antioxidant activities in food and in-vitro studies and showed higher activity in trapping lipophilic electrophiles and reactive nitrogen and oxygen species. The lower plasma levels of γ- compared to α-tocopherol might be discussed in the light of different bioavailability, but also in a potential transformation from γ- into α-tocopherol. From the metabolism end product, only that of γ-tocopherol (2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman), but not that of α-tocopherol, was identified to provide natriuretic activity. Studies also indicate that only the γ-tocopherol plasma level served as biomarker for cancer and cardiovascular risk. Therefore, this paper provides a comprehensive review on γ-tocopherol with emphasis on its chemistry, biosynthesis, occurrence in food, different intake linking to different plasma levels in USA and Europe, absorption and metabolism, biological activities, and possible role in human health.