Exogenous hormones are widely prescribed in the United States, primarily as oral contraceptives and hormone-replacement therapy. Each of these frequently used categories of drugs has important potential for altering risk of several major human cancers. The efficacy of oral contraceptives in preventing ovarian cancer and endometrial cancer is well established. There remains controversy about the relationship between oral-contraceptive use and breast cancer risk, but most studies show that use in the postmenarcheal and perimenopausal periods is associated with an increased risk of breast cancer in a duration-dependent manner. As with oral contraceptives, the relationship between estrogen-replacement therapy and breast cancer risk is controversial, but several well-designed studies showed a moderate increased risk after long-term use. Estrogen-replacement therapy is a major cause of endometrial cancer. Combination hormone-replacement therapy will probably reduce some of the excess risk of endometrial cancer, but few epidemiological data exist on this relationship. The sparse data suggest that combination therapy may enhance breast cancer risk. As with endometrial and ovarian cancers, hormonal chemoprevention of breast cancer is also feasible. We review two such strategies, ie, gonadotropin-releasing hormone agonists and the antiestrogenic drug tamoxifen.