The involvement of estrogen and its receptors in the development of cancer has been known for years. However, the exact mechanism responsible is far from clear. The estrogen-mediated carcinogenic process is complicated by recent findings, which reveal that estrogens have multiple functions in cells, which can be either adverse or beneficial, and that the effects of estrogen may be cell-type or organ dependent. The estrogenic effect may be also greatly influenced by the state of two estrogen receptors, ERalpha and ERbeta. This review will discuss the role and function of estrogens and its receptors in cancers of three categories: (1) Breast cancer and gynecologic cancers, (2) Cancers of endocrine organs, (3) Lung cancer and cancers of digestive system. We will also review some novel treatments aiming to interfere with relevant pathways mediated by estrogens and its receptors.