Objective: To identify which patients with prostate cancer are at high risk for local or distant recurrence after radical prostatectomy. Methods: Review of data from several historical and contemporary series of patients undergoing radical prostatectomy. Results: Patients with high-grade disease (i.e., Gleason score ≥8), positive margins, and seminal vesicle invasion have relatively high risks of biochemical and clinical failure if no adjuvant therapy is given. Use of radiation therapy may improve local control rates for a subset of these patients(i.e., those with positive margins) but appears to have little impact on the later development of metastatic disease or of prostate cancer death. Hormone therapy may delay the onset of failure for other patients with ‘high-risk’ disease but there are few data to support its widespread use. Conclusions: Enhanced ability to predict which patients with high-risk prostate cancer will fail locally after radical prostatectomy is needed. Such patients should then be enrolled in a randomized study of postoperative adjuvant radiation therapy. Similarly,patients predicted to be at high risk for distant failure should be enrolled in trials evaluating conventional and ‘novel’ forms of hormonal therapy (i.e.,potency sparing regimens) to determine whether such therapy delays the time to biochemical or clinical progression without compromising the patient’s quality of life.