Perhaps not surprisingly, vitamin E which has been touted to be potentially beneficial for a variety of disorders, including cancer, heart disease, and even Alzheimer's disorder, based on its function as an antioxidant has failed to withstand the scrutiny of recent, double-blinded, placebo-controlled clinical trials, including failure to provide science-based support for vitamin E as a potent anticancer agent. Although less studied, vitamin E forms other than RRR-alpha-tocopherol or synthetic all-rac-alpha-tocopherol show promise as anticancer agents in preclinical studies. This chapter will (1) review basic information about natural and synthetic vitamin E compounds as well as vitamin E analogues, (2) summarize the current status of human intervention trials, (3) review data from preclinical cell culture and animal model studies of vitamin E compounds and novel vitamin E-based analogues in regards to future potential for cancer treatment, and (4) summarize some of the insights that have been gained into the anticancer mechanisms of action of vitamin E-based compounds which are providing interesting insights into their potent proapoptotic effects, which include restoration of apoptotic signaling pathways and blockage of prosurvival signaling events.