Hormonal therapy, such as tamoxifen (TAM), is the cornerstone of adjuvant treatment for women with surgically resected early breast cancer that is hormone receptor-positive (HR+), typically defined by breast tumors that express the estrogen receptor (ER), the progesterone receptor (PgR), or both. TAM can have both estrogen-antagonistic and estrogen-agonistic effects, and expression of growth factor receptors such as human epidermal growth factor receptor (HER)2 in breast cancer is associated with the development of TAM resistance. Studies also suggest that a lack of PgR expression in tumors with positive ER status may be associated with increased growth factor expression, a more aggressive tumor phenotype, and TAM resistance. The aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane have proven more effective than TAM as adjuvant hormonal therapy in postmenopausal women with HR+ disease. Some translational studies have also begun to investigate the efficacy of hormonal therapy according to PgR or HER2 status of the tumor. The AIs have proven to be an attractive option for patients across a broad spectrum of receptor expression profiles, and the potential for combination therapy using AIs and specific growth factor inhibitors is also under investigation.