Bone metastases are a common problem for breast cancer patients, causing significant disease-related morbidity and mortality. Bisphosphonates and other cancer therapies can assist in managing these patients. However, assessing treatment efficacy in bone metastases is hampered by the inability to accurately measure disease response within a clinically desirable time frame. Bone-specific biochemical markers, notably type I collagen telopeptide cross-link by-products such as N-telopeptide (NTx) and C-telopeptide (CTx), have been shown to be effective tools for assessing the severity and extent of bone metastases, and the response to bisphosphonates. Elevated NTx levels correlate with adverse clinical outcomes. Normalization of NTx and CTx excretion rates are associated with relief of symptoms and a reduced incidence of skeletal-related events (SRE). This review discusses the expanding role of these bone markers in guiding treatment of bone metastases from breast cancer.