Estrogen-dependent growth of some breast cancers was a key observation, which led to the development of tamoxifen and aromatase inhibitors (AIs). Tamoxifen and AIs have different modes of action and side-effect profiles. Based on evidence, both in laboratory models and clinical trials, longer duration of hormone suppression therapy is beneficial. The most important factor deciding their use is "menopausal status." Sometimes, defining menopause might be challenging in clinical practice. Measuring serum follicle stimulating hormone (FSH) and estradiol levels are helpful when in doubt. Tamoxifen should be offered to those women with normal FSH and estradiol levels even with cessation of menstruation. Once menopause is defined, it is relatively clear to decide about the endocrine therapy. Premenopausal women should be treated with tamoxifen and postmenopausal women with AIs. Perimenopausal women should be treated with tamoxifen initially and later switched to AIs once they become postmenopausal. With current recent evidence, premenopausal women should be treated with 10 years of tamoxifen. Current evidence also supports 5 years of an AI alone or 5 years of tamoxifen followed by 5 years of an AI; studies evaluating longer duration of AI treatment are in progress (Figure 1). Compliance with long-term use of these adjuvant endocrine therapies depends on screening for and management of side effects. Patients taking tamoxifen should be clinically screened for thromboembolism and for endometrial cancer if abnormal bleeding occurs. Patients on AI should pay careful attention to management of other chronic health disorders. They also should be screened for optimal bone health. Management of vasomotor symptoms also helps with adherence to long-term treatment for both tamoxifen and AIs. © 2013 Springer Science+Business Media New York.