Besides their potent antioxidant activity, vitamin E isoforms demonstrated multiple therapeutic activities among which is their activity against different cancer types, including breast, prostate, and colon cancers. However, the activity of vitamin E isoforms is limited by their low bioavailability following oral administration. In addition to the low solubility, vitamin E isoforms have been established as substrates for several intestinal and hepatic transport proteins. In this review, we present reported anticancer activity of vitamin E family members and the possible utilization of vitamin E and derivatives as chemosensitizers to reverse multidrug resistance when given as part of a delivery system and/or in combination with anticancer therapeutic drugs. Then, the review discusses disposition of vitamin E members and transport proteins that play a role in determining their systemic bioavailability followed by recent advances in vitamin E formulations and delivery strategies.