Vitamin E is an important nutrient with antioxidant and non-antioxidant functions, and certain evidence suggests that it has a cardiovascular protective role. It is therefore important to maintain an optimal vitamin E status. In the present paper, a number of MS applications to monitor vitamin E status and its interactions, including the use of stable-isotope-labelled vitamin E and metabonomics, are highlighted. Specifically, stable-isotope studies have been used to monitor vitamin E absorption, hepatic processing and lipoprotein transport. As oxidative stress may influence vitamin E status, a number of studies comparing vitamin E biokinetics and metabolism in cigarette smokers and non-smokers have been able to show differences in vitamin E processing in smokers. Metabonomics represents a method to identify changes to metabolite profiles, offering the potential to investigate interactions between vitamin E and metabolic pathways. These applications represent innovative approaches to investigate the role of vitamin E in health and disease.