Although 90% of men with advanced prostate cancer respond to initial therapy with castration, orchiectomy or a luteinizing hormone-releasing hormone agonist. At progression, about one third respond to addition of an anti-androgen (e.g. flutamide, bicalutamide) and of those respond and then progress about 20% respond to withdrawal of the anti-androgen. Hormone manipulation in men with prostate cancer may lead to impotence, gynecomastia, hot flashes, osteoporosis, sarcopenia, anemia, and an increased risk of cardiovascular events. Initiation of androgen deprivation therapy at rise in prostate-specific antigen versus development of symptomatic metastases, maximum androgen blockade versus castration alone, and the use of continuous versus intermittent hormone therapy remain controversial. In patients with asymptomatic castration-resistant prostate cancer (CRPC), sipuleucel-T (an autologous cellular immunotherapy) has been shown to extend median survival. In patients with symptomatic CRPC, docetaxel plus prednisone is established as the preferred first-line chemotherapy since it provides a survival benefit. Men who have failed docetaxel-based chemotherapy can be treated with cabazitaxel (a microtubule-interacting agent), abiraterone acetate (a CYP17 [androgen biosynthesis pathway] inhibitor), enzalutamide (an androgen receptor antagonist), or radium-223 chloride. In men with castration-resistant prostate cancer who have bone metastases, denosumab (a receptor activator of nuclear factor-kB ligand inhibitor) and zolendronic acid (a bisphosphonate) have been shown to prevent pathologic fracture, spinal cord compression, or the need for surgery or radiotherapy to bone.