Prostate cancer (PC) is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death among American men. Bone is by far the most common site for metastasis. The median survival of patients from the development of bone metastases is ~3 years. During this period, patients are at increased risk of skeletal-related events (SREs) including: intractable bone pain, pathological fractures and spinal-cord compression. Several novel bone-targeted agents including bisphosphonates, receptor activator of nuclear factor κB (RANK) ligand monoclonal antibodies, endothelin receptor antagonists, bone-seeking radioisotopes, selective estrogen receptor (ER) modulators and tyrosine kinase inhibitors are now available and under evaluation in clinical trials in PC patients with bone metastases. This review article will provide an overview of the multiple emerging novel bone-targeted therapies in PC.