Aromatase inhibitors (AIs) have become integral to the treatment of women with breast cancer and are the treatment of choice in postmenopausal women who have tumors that are estrogen receptor positive. The depletion of estrogen seen with AI therapy is significant and translates to beneficial tumor effect but has a negative impact on skeletal bone. Bone loss incurred from AI use creates an increased risk for osteoporosis and subsequent bone fractures. Menopausal women have additional bone loss when using AIs. In addition, younger women may develop risk for osteoporosis as a result of premature menopause from other therapies used in the treatment of breast cancer. The process by which a woman treated for breast cancer develops osteoporosis differs from the bone loss that occurs from menopause alone and should be considered as a separate process. The effects of AI therapy on women with breast cancer are profound, and patients may require specialized approaches to therapy. This article will discuss osteoporosis, including assessment and diagnosis, and review the available and experimental treatments, as well as nursing implications in the treatment of women with breast cancer on AI therapy.