Although much progress has been made in the four years since the first edition of Management of Prostate Cancer, prostate cancer remains a significant biological, me- cal, and personal challenge for millions of men. In this interval, some important trends and observations have emerged that represent real progress in the field and which will shape the direction of clinical practice and research in the next 5–10 years. These obs- vations include: (1) a decline in prostate-related cancer mortality in the United States, likely owing to a combination of factors including screening, more aggressive and earlier therapy, and improvements in specific therapies; (2) a significant downward pathological stage migration, so that an individual’s chance of cure for a given stage, grade, and PSA is better now than it was early in the PSA era, even without associated improvements in individual therapies; (3) the recognition of new PSA isoforms that may refine screening strategies; (4) several randomized, phase III clinical trials demonstrating survival adv- tages of one form of therapy over another in selected populations (external beam rad- therapy with adjuvant hormones vs radiotherapy alone, radical prostatectomy vs observation); (5) a focus on the biology of bone and bone metastasis, and new agents that reduce skeletal-related events and which may inhibit the growth of new metastases; (6) second-generation anti-PSMA antibodies with improved potential for imaging and therapy; (7) the development and widespread adoption of nomograms that assist in cli- cal decision-making for individual patients; (8) the identification of new genes that