For patients undergoing radical prostatectomy for prostate adenocarcinoma, the most common cause of failure is an asymptomatic increase in levels of prostate-specific antigen (PSA). Salvage radiotherapy (RT) to the prostate bed has been used when there is no clinical evidence of metastatic disease. However, this is still not widely accepted because there is currently no consensus on the optimal management of an isolated PSA failure. Salvage RT given in a select group of patients is effective, with a 70% to 80% biochemical response rate and a long-term biochemical control rate as high as 35% to 40%. These data indicate that RT offers a substantial risk of curative salvage of patients who fail radical prostatectomy. Although there is interest in studying investigational modalities (eg, vaccine therapy) among patients with asymptomatic, PSA-detected recurrences after surgery, caution must be applied, and treatment modalities with known curative potential (ie, RT) should be used before noncurative techniques are attempted. This article outlines the rationale, results, and toxicity of salvage RT for an asymptomatic increase in PSA levels, with emphasis on identifying patients with favorable prognostic factors with higher rates of long-term biochemical control with local treatment.