Hormonal therapy is the first line of treatment for hormone receptor (HR)-positive breast cancer, which accounts for approximately two thirds of all breast cancers. The HR-positive breast cancers are characterized by dependence on estrogen for their growth; hence, therapeutic strategies have been developed to inhibit hormone-mediated tumor growth. For over 25 years, the selective estrogen receptor modulator tamoxifen has been the mainstay in the hormonal treatment therapy of breast cancer. More recently, third-generation aromatase inhibitors/inactivators (AIs), potent agents that suppress estrogen production, are being integrated into adjuvant treatment regimens. Questions remain regarding the optimal strategy for utilizing AIs in the adjuvant setting, and ongoing trials will investigate their timing and duration of use as well as further characterize their side-effect profiles and their long-term impact on quality of life.