Prostate cancer is the second most commonly diagnosed cancer and the third leading fatal cancer in American men. Comprehensive studies from human epidemiological studies, animal tumor models, and cellular molecular levels suggested that alpha-vitamin E and its derivatives possess remarkable chemopreventive and chemotherapeutic against prostate cancer. This chapter details the facts of alpha-vitamin E and its nonantioxidant functions in prostate cancer, focuses on the biological mechanisms for the alpha-vitamin E and its ester analogue, alpha-vitamin E succinate (VES), in prevention and therapy of prostate cancer, and raises specific questions that remain for intensive investigation in the future.