In 2006, invasive breast cancer is estimated to be diagnosed in 212,920 women and 1,720 men in the US, thus affecting women at a rate almost 200 times that of men. The description of breast tumors as a primary phenomenon of the female gender is documented in medical writings dating as far back as those contained in the ancient Egyptian papyrus acquired by Edwin Smith, which document cases of breast tumors as early as 1600 B.C. It would take nearly 2,000 years to recognize that the predominance of breast disease in women had a relationship to the chemical differences that exist between women and men. Of the 212,920 women to be diagnosed with breast cancer in 2006, 163,948 will be postmenopausal. The editors hope that the articles in this publication will highlight the challenges of determining the mechanistic basis for the role of hormones in the etiology of postmenopausal breast cancer and bring attention to the advancements and challenges still facing effective prevention and treatment of this disease.