Estrogens are synthesized in the gonads and extra-gonadal organs and play important roles in regulating the development and function of reproductive organs as well as other functions. Estrogens exert their functions by binding to nuclear receptors, membrane receptors, or cytoplasmic proteins. Antiestrogens are agents that either inhibit estrogen production or interfere with estrogen receptor (ER) signaling, thereby preventing estrogens from mediating their biological actions. In females, antiestrogens are widely used to treat ER-positive breast cancers because lowering estrogen levels or ER signaling inhibits tumor growth and prevents remission. However, unintended exposures to antiestrogens disrupt the synthesis and actions of estrogens, threatening the health of the exposed individuals. This chapter discusses natural and medical antiestrogens and their uses in breast cancer therapy. Also discussed are the impacts of antiestrogens as environmental endocrine disruptors on the female reproductive functions.