Cancer treatment has advanced and survivorship is increasing. As such, a new skeletal complication of malignancy, cancer treatment-induced bone loss, has emerged and is likely to be the most common skeletal complication of malignancy in years to come. Therapy for the most common cancers, breast and prostate, often results in sex-steroid deficiency and subsequent bone loss. A significant portion of breast cancers express estrogen receptors, and estrogen stimulates tumor growth. Therapy directed against estrogen action or to reduce estrogen production results in significant survival advantage in women with estrogen receptor-positive breast cancer. This hormonal therapy represents the mainstay of breast cancer treatment and is highly effective. Many breast cancers are also treated with chemotherapy, which often induces transient or permanent ovarian failure. However, estrogen is a critical factor for maintaining bone health and normal bone mineral density. As such, all of these breast cancer therapies may induce bone loss, mainly by reducing estrogen or its action on bone. Aromatase inhibitors fall into this category; its efficacy dictates that it will become first-line therapy for most hormone-sensitive breast cancers. Theoretically, chemotherapy may have direct effects on bone that are independent of the effects of estrogen deficiency, but evidence is lacking. Limited clinical experience indicate that bisphosphonates are effective in preventing bone loss owing to cancer treatment. This article focuses on therapy for breast cancer and other malignancies and the respective contributions of such therapy to bone loss.