Today, more men than ever before are being followed after radical prostatectomy. Prognosis and follow-up should be based on the pathologic specimen. Measurable prostate-specific antigen (PSA) after surgery defines failure, with time to detectable PSA and rate of PSA rise being useful prognostic factors. The natural history of untreated biochemical failure is protracted, a fact to be considered in discussions of adjuvant treatment. Early in disease recurrence, imaging studies to locate residual disease rarely are useful clinically. Both adjuvant and salvage radiation to the prostate bed have benefits and risks, but neither is superior in overall prostate cancer survival. The timing of hormone therapy remains largely empiric. The promise of effective cytotoxic chemotherapy still is greater than its actual benefits, although novel cytostatic agents are being developed. The future management of this disease will improve with better molecular definition of risk and therapeutic response.