The treatment of women with estrogen receptor-positive breast cancer has advanced significantly in the past decade. Tamoxifen was the gold standard hormonal therapy for breast cancer until the introduction of aromatase inhibitors and fulvestrant. Many of these new treatments are useful only for patients who are postmenopausal. There are data to support the use of these new agents both in the metastatic and adjuvant settings. Here, we briefly review the recent clinical trials supporting the use of these agents in both the adjuvant and metastatic settings. We will discuss possible mechanisms of resistance to endocrine agents that could be exploited therapeutically to improve the outcome for patients with hormone receptor-positive breast cancers.