Current therapies have extended the survival of patients with prostate cancer. However, these patients often develop skeletal morbidity from disease- and treatment-related effects that undermine skeletal integrity throughout the course of the disease. Low bone mineral density (BMD) is prevalent in patients with early-stage prostate cancer, and androgen-deprivation therapy by either pharmaceutical agent (including hormonal) or surgical castration causes significant decreases in BMD. Fractures can result in a loss of independence and have been associated with shorter survival in patients with prostate cancer. Zoledronic acid is the only bisphosphonate that has demonstrated objective and long-term benefits in reducing skeletal morbidity in patients with bone metastases due to prostate cancer, and it has produced long-term reductions in pain levels compared with placebo in this setting. Therefore, bisphosphonates, particularly zoledronic acid, may provide important benefits for preserving bone health during the course of prostate cancer progression.