Hormonal manipulation in the form of androgen-deprivation therapy for prostate cancer was introduced by Huggins and Hodges in 1941 and resulted in a Nobel Prize in 1966. Hormonal therapy initially had been used in metastatic prostate cancer, but the indications have been expanded including failed local therapy, locally advanced prostate cancer, and neoadjuvant or adjuvant therapy in high-risk localized prostate cancer. In view of the magnitude of the problem of prostate cancer and relatively frequent use of hormonal manipulation, it is important for clinicians to be aware of common side effects, prevention, and treatment to improve quality of life and reduce morbidity and mortality in patients with prostate cancer. This review focuses on the common side effects of hormonal treatment such as osteoporosis, anemia, hot flashes, erectile dysfunction, muscle wasting, gynecomastia, decline in cognitive function, depression, increase in body fat and metabolic changes, and their prevention and treatment. © 2005, Current Science Inc.