Knowledge of bone metastases complicating advanced prostate cancer (CaP) is increasingly relevant in patient selection for novel therapies. Current nuclear bone scintigraphy imaging has limited specificity for prostate metastases. As serum bone markers do correlate with bony lesions, they may play multiple roles in patients with advanced CaP. Currently, these markers play a role in prognostic nomograms for CaP. Recent studies suggest an expanding role for bone markers in the diagnosis and selection of patients for novel therapies. In the future, therapeutic roles for some of these marker pathways will emerge, eventually allowing greater individualization of patient care.